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Intervention using vitamin D for elevated urinary albumin in type 2 diabetes mellitus (IDEAL-2 Study): study protocol for a randomised controlled trial
The prevalence of type 2 diabetes mellitus (T2DM) is increasing worldwide. T2DM is associated with serious macro- and microvascular complications. In particular, diabetic kidney disease (DKD), which begins with excessive urinary albumin excretion, has a significant impact on affected individuals and is costly to healthcare services. Inhibition of the renin–angiotensin–aldosterone system (RAAS) with angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) significantly reduces albuminuria in diabetes, but this effect is not observed in all those treated. Active vitamin D analogues have been observed to be reno-protective through inhibition of RAAS in animal and human studies. Therefore, it can be hypothesised that an active vitamin D analogue will have an additional benefit to ACEI/ARB treatment for albuminuria reduction in DKD.
The planned study is an ongoing non-blinded randomised controlled parallel-group trial examining the impact, in individuals with T2DM, of the addition of bioactive vitamin D (calcitriol) to RAAS inhibition treatment using ACI or ARB on urinary albumin excretion over a period of 26 weeks. The primary outcome measure is the urinary albumin creatinine ratio. It is planned for the study to recruit 320 participants. Other outcome measures of interest include 24-h urine albumin (24 h UA) excretion, estimated glomerular filtration rate (eGFR), blood pressure and quality of life. Safety will be assessed throughout.
If the addition of calcitriol to RAAS inhibition with ACEI or ARB safely results in a significant reduction in albuminuria, the study adds to the body of evidence supporting a role for vitamin D in reno-protection, will inform clinical practice and could result in significant reduction of healthcare costs associated with DKD.
Trial registration
ISRCTN, ISRCTN86739609. Registered on 7 June 2017. ClinicalTrials.gov, NCT03216564. Registered on 13 July 2017.
KeywordsType 2 diabetes mellitus Diabetic kidney disease Albuminuria Angiotensin converting enzyme inhibitor Angiotensin receptor blocker Vitamin D
- 24 h UA
24-h urine albumin
Angiotensin converting enzyme
Angiotensin converting enzyme inhibitor
Albumin-creatinine ratio
Angiotensin receptor blocker
Chronic kidney disease
Case report forms
C-reactive protein
Diabetic kidney disease
- eGFR
Estimated glomerular filtration rate
Euroquol 5D
End-stage renal disease
- HbA1c
Glycated haemoglobin
International Committee of Medical Journal Editors
- IgA
Immunoglobulin A
Institutional review board
Modification of Diet in Renal Disease
- miRNA
Michigan Neuropathy Screening Instrument
- mRNA
Messenger RNA
National Priorities Research Program
Parathyroid hormone
Qatar National Research Fund
Renin angiotensin aldosterone system
Randomised controlled trial
Systolic blood pressure
Type 2 diabetes mellitus
- TGF-β
Transforming growth factor β
Total iron binding capacity
The prevalence of type 2 diabetes mellitus (T2DM) has reached pandemic proportions. T2DM is syndemic with obesity, whose prevalence has also increased dramatically worldwide. T2DM is associated with macrovascular (ischaemic heart disease, stroke and peripheral vascular disease) and microvascular (nephropathy, retinopathy and neuropathy) complications. Of those with diabetes, 30–50% will develop kidney disease and are at risk of progressing to end-stage renal disease (ESRD) [1]. Diabetic kidney disease (DKD) is the leading cause of ESRD worldwide [1, 2]. Once ESRD occurs, there is a significant individual burden of increased cardiovascular risk and reduced quality of life as well as requirement for renal replacement therapy and transplantation with increased healthcare costs.
Renin–angiotensin–aldosterone system (RAAS) blockade with an angiotensin converting enzyme (ACE) inhibitor (ACEI) or angiotensin II type I receptor blocker (ARB) is the most widely used strategy to slow the progression of DKD in both type 1 diabetes mellitus [3] or T2DM [4, 5]. RAAS blockade reduces blood pressure, the mean rate of decline in glomerular filtration rate (GFR) by 2–10 mL/min per year and albuminuria in DKD [4, 5]. However, not all those treated achieve adequate control of blood pressure, a reduction in albuminuria or prevention of a decline of renal function [6].
Several mechanisms, including polymorphisms in the ACE gene, have been proposed to account for the variability of response to RAAS therapy [7]. An emerging hypothesis is that RAAS blockade leads to compensatory stimulation of the RAAS, contributing to therapy resistance [8]. Thus, therapeutic approaches directed at suppression of the compensatory increase in the RAAS are increasingly sought [9].
Experimental and clinical evidence suggest that vitamin D may be reno-protective in chronic kidney disease (CKD), including DKD [10, 11, 12, 13, 14, 15]. In animal models of glomerular injury, 1,25-dihydroxycholecalciferol (1,25-(OH)2-D3; calcitriol) ameliorates glomerular injury [16] and enhances renal protection by suppressing transforming growth factor β (TGF-β)-induced α-smooth muscle actin production and type 1 collagen [17], and by increasing hepatocyte growth factor [17]. Vitamin D analogues have been reported to decrease glomerular podocyte loss and podocyte hypertrophy [18]. 1,25-(OH)2-D3 is a negative regulator of the RAAS. Vitamin D deficiency stimulates renin expression in normal mice and injection of 1,25-(OH)2-D3 reduces renin synthesis [18]. Rats with the remnant kidney model of CKD treated with the vitamin D2 analogue paricalcitol (19-nor-1,25-dihydroxyvitamin D2) showed reductions of 30–50% in kidney tissue messenger RNA (mRNA) and protein levels of angiotensinogen, renin, renin receptor and vascular endothelial cell factor, and amelioration of glomerular damage and proteinuria compared to untreated rats [19]. Diabetic mice lacking the vitamin D receptor develop more severe nephropathy than wild-type mice suggesting that vitamin D is reno-protective by suppressing the RAAS [19]. Zhang et al. demonstrated that combination therapy with the AT1 receptor blocker losartan and paricalcitol prevented albuminuria, restored glomerular filtration barrier structure and reduced glomerulosclerosis in diabetic mice, and that these changes were associated with suppression of intra-renal renin and angiotensin II, as well as transforming growth factor- β (TGF-β) [19, 20]. This group reported similar and long-term suppression of the RAAS and reduction of proteinuria using another vitamin D2 analogue, doxercalciferol, in experimental diabetic nephropathy [21]. In humans, observational data suggest an inverse relationship between serum 25-hydroxyvitamin D levels and both albuminuria [22] and progression of CKD [23]. Small, clinical studies show that vitamin D therapy may be useful in reducing glomerular injury in IgA nephropathy and CKD [24, 25, 26]; a secondary analysis of clinical trials of paricalcitol therapy suggested that this agent is associated with a reduction of proteinuria in individuals with various forms of CKD [27]. In a randomised clinical trial (VITAL study), de Zeeuw et al. reported that the addition of paricalcitol to RAAS inhibition safely reduces albuminuria in those with T2DM [28].
Study rationale
The striking histologic, molecular and hormonal improvements observed with vitamin D in experimental kidney disease, coupled with promising preliminary clinical results observed in humans, provides the rationale for the IDEAL-2 (Intervention using vitamin D for elevated urinary albumin in type 2 diabetes mellitus) study. IDEAL-2 is a non-blinded randomised controlled trial (RCT) aiming to examine the impact of the addition of the active form of vitamin D (1,25-(OH)2-D3; calcitriol) to ACEI or ARB in T2DM individuals with albuminuria. Calcitriol was chosen as the active form of vitamin D because of its availability in Qatar.
Our primary hypothesis is that bioactive vitamin D (1,25-(OH)2-D3 [calcitriol]), added to inhibition of the RAAS, via ACE inhibition or ARB, has a differential impact on urine albumin excretion in T2DM compared to RAAS inhibition alone.
Primary objective
The primary objective of IDEAL-2 is to examine the effect of calcitriol + ACEI or ARB therapy on urine albumin to creatinine ratio (ACR; measured in a standard clinical biochemistry laboratory) compared to ACEI or ARB therapy alone, after 26 weeks, in individuals with type 2 diabetes (T2DM).
Secondary objectives
- 1.
24-h urine albumin (24 h UA) excretion;
- 2.
Estimated glomerular filtration rate (eGFR);
- 3.
Blood pressure;
- 4.
Quality of life (measured using the EQ-5D questionnaire).
Tertiary objectives
Diabetes complications
The study will examine the impact of the interventions on other diabetes complications. Neuropathy will be assessed using the Michigan Neuropathy Screening Instrument (MNSI) [29, 30] and physical examination. Retinopathy will be assessed through retinal photography. The Vicorder device will be used to assess measures of arterial stiffness [31].
The study will examine circulating and urinary biomarkers associated with disease severity, disease progression and treatment response. A key objective is to develop urinary mRNA/microRNA (miRNA) biomarkers predictive of response to therapeutic interventions. Our assessment of urinary mRNA and miRNA may also provide mechanistic insights into the disease process as well as suggest mechanisms for the therapeutic outcomes. We will perform mRNA and miRNA profiling of urine collected before randomisation (baseline) and at 26 weeks of treatment and investigate whether urinary cell mRNA/miRNA profiles are associated with baseline albuminuria and eGFR in the individuals enrolled in the study and whether the urinary cell mRNA/miRNA profiles are associated with changes in albuminuria and eGFR following intervention. Our urinary mRNA profiling strategy has been successfully adapted by others to predict disease activity and progression of native kidney disease including diabetic nephropathy [32, 33]. We will utilise this assay for the measurement of urinary cell levels of mRNAs for proteins implicated in diabetic nephropathy (e.g. TGF-β1), mRNAs that may be regulated by vitamin D (e.g. renin) and podocyte-associated mRNAs (e.g. podocin). We have previously demonstrated the clinical utility of urinary cell profiles in renal allograft recipients [34, 35, 36, 37, 38, 39].
Podocyte-specific loss of functional miRNAs in mice results in proteinuria, glomerular and tubular injury, renal failure and death [40, 41, 42]. miR-192 and miR-377, both upregulated by TGF-β1 in mesangial cells, are hyper-expressed in mouse models of diabetic nephropathy [41, 42]. Recently, TGF-β1 and β2 were shown to downregulate miR-200a, a miRNA with potential for preventing renal fibrogenesis [43]. Also, a loss of miR-192 has been associated with fibrogenesis in humans [44]. Wang et al. recently reported that urinary levels of miR-200a-200b and -429 are low in individuals with IgA nephropathy compared to healthy controls, and that 'the degree of reduction correlated with disease activity and rate of progression'. Moreover, an inverse association of urinary expression of ZEB2 mRNA with miR-200b and that of vimentin mRNA with miR-200a was observed [45].
IDEAL-2 is an ongoing non-blinded randomised controlled parallel-group trial examining the impact of the addition of bioactive vitamin D (calcitriol) to RAAS inhibition treatment using ACEI or ARB on urinary albumin excretion. The reported protocol follows the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) recommendations (http://www.spirit-statement.org/; see Additional file 1: SPIRIT checklist).
Sponsor and funding
The study is sponsored by Hamad Medical Corporation, Qatar. The study is funded by the Qatar National Research Fund (QNRF) through the National Priorities Research Program (NPRP) grant NPRP 4–1392–3-345. Support is also provided by the Clinical Research Core at Weill Cornell Medicine in Qatar, supported by the Biomedical Research Program funded by Qatar Foundation. There is no input from the funding or sponsor organisations into the design, conduct, analysis or reporting of the study.
Study design
- 1.
A[−]Calcitriol: ACEI/ARB alone (the usual standard care for diabetic albuminuria);
- 2.
A[+]Calcitriol: ACEI/ARB + calcitriol.
In the A[+]Calcitriol group, participants will receive calcitriol 0.25 μg daily and optimised ACEI/ARB for 26 weeks. Adjustment of treatment will be based upon safety endpoints and if emerging data shows any evidence of safety concern.
In the A[−]Calcitriol group, participants will receive conventional therapy with ACEI/ARB for 26 weeks. Adjustment to the dosage of ACEI or ARB will be based upon safety endpoints and if emerging data show evidence of safety concern.
Drug dosages
- 1.
ACEI/ARB: It is expected that participants will be optimised for ACEI/ARB treatment by achieving the maximum recommended dose or, if this is not possible, the maximal tolerated dose.
- 2.
Calcitriol: The dose of calcitriol employed in the study is 0.25 μg (250 ng) orally per day. If the calcium level is 2.62–2.79 mmol/L in the calcitriol + ACEI/ARB group and the participant is taking calcitriol 0.25 μg daily, the individual will decrease calcitriol to 0.25 μg thrice weekly. Calcium levels will be rechecked in two weeks. If the follow-up calcium level continues to be ≥ 2.62 mmol/L, the participant will discontinue use of calcitriol for the remainder of the study. If the follow-up calcium level is < 2.62 mmol/L, the individual will continue calcitriol 0.25 μg thrice weekly. If subsequently the calcium level is > 2.62 mmol/L in the calcitriol + ACEI or ARB group and the participant is taking calcitriol 0.25 μg thrice weekly, the individual will be withdrawn from the study intervention. In the unlikely event that the repeated serum calcium level is ≥ 2.62 mmol/L in the ACEI or ARB alone group at any stage, the investigator will consider withdrawing the participant from the study and investigating this clinically.
Recruitment and setting
Individuals will be identified, screened for eligibility and recruited from the Hamad Medical Corporation outpatient clinics. Hamad Medical Corporation is the main clinical care provider in Qatar and consists of general and specialist hospitals providing secondary and tertiary care. Participants will be identified by clinicians in the outpatient department; if they are interested in participating in the study, they will be scheduled for a screening visit. The clinician will ensure that all clinically routine blood and urine tests have been conducted to allow assessment of participant eligibility and participation. Written informed consent is taken by a trained member of the research team independent of the referring physician.
Eligibility criteria
The eligibility criteria are designed to include individuals appropriate for the study protocol. All relevant medical and non-medical conditions will be taken into consideration by the investigator team on whether the protocol is appropriate for an individual participant.
Inclusion criteria
- 1.
Age ≥ 18 years and < 80 years.
- 2.Diagnosis of T2DM requiring treatment with at least one oral hypoglycaemic medication or insulin:
- a.
Individuals will be considered to have established T2DM if the diagnosis of diabetes has been made and the participants were treated an oral hypoglycaemic agent or with insulin or for at least six months after diagnosis;
- b.
Individuals will be considered to have newly established T2DM if the diagnosis of diabetes was diagnosed with a fasting plasma glucose ≥ 7 mmol/L (126 mg/dL) or haemoglobin A1c is > 6.5% in the past six months;
- c.Documented albuminuria, defined as a presence of albuminuria on two occasions in the last six months:
- i.
A spot-urine ACR ≥ 30 mg/g creatinine (≥ 2.5 mg/mmol creatinine in men, ≥ 3.5 mg/mmol creatinine in women), or
- ii.
Albumin ≥ 30 mg/24 h in a 24-h urine collection, or
- iii.
Albumin ≥ 20 μg/min in a short-time urine collection, or
- iv.
Albumin ≥ 30 mg/L in a spot-urine sample.
- i.
- a.
- 3.
eGFR using the four-variable Modification of Diet in Renal Disease (MDRD) equation of ≥ 25 mL/min/1.73 m2.
Exclusion criteria
- 1.
If female: positive pregnancy test or planning pregnancy in the subsequent 12 months.
- 2.
- 3.
- 4.
Corrected serum calcium ≥ 2.62 mmol/L.
- 5.
Serum potassium > 5.2 mmol/L if not on ACEI or ARB; serum potassium > 6.0 mmol/L if on ACEI or ARB.
- 6.
25-hydroxyvitamin D (25-OH Vit D) > 80 ng/mL.
- 7.
PTH > 200 pg/mL.
- 8.
Poorly controlled hypertension defined as systolic blood pressure (SBP) ≥ 180 mmHg or diastolic blood pressure ≥ 110 mmHg.
- 9.
SBP ≤ 110 mmHg.
- 10.
History of kidney stones.
- 11.
History of severe chronic disease (e.g. chronic liver disease).
- 12.
Active malignancy.
- 13.
Recent diagnosis of acute renal failure within three months of screening visit.
- 14.
Likelihood of renal replacement therapy within one year.
- 15.
Any clinical and biochemical indication of primary hyperparathyroidism.
- 16.
History of parathyroidectomy.
- 17.
History of chronic diseases of malabsorption (e.g. Crohn's disease, coeliac disease).
- 18.
History of cystic fibrosis.
- 19.
Currently taking calcitriol.
- 20.
Currently taking calcitonin, bisphosphonates, cinacalcet, teriparatide, glucocorticoids or other drugs that may affect calcium or bone metabolism (individuals may be taking calcium containing phosphate binder or other phosphate binder. Individuals may also be taking stable dose of oestrogen/progestin).
- 21.
Currently taking digitalis (cardiac glycosides).
- 22.
Clinical history of osteoporosis or other bone disorder and currently on calcitriol therapy.
- 23.
History of allergic reaction to calcitriol, paricalcitol or other 1,25-dihydroxyvitamin D analogues.
- 24.
History of allergic reaction to any ACEI or ARB therapy.
Participation in the study will also take into account any clinical contraindications that may preclude participation as determined by the individual's physician or the investigator team.
Those who are clinically determined to have an active infection during any urine collection will have the urine test within one week after the resolution of the infection.
Female participants and pregnancy
- 1.
A physician documented history of hysterectomy (removal of the womb) and/or bilateral oophorectomy (removal of both ovaries); or
- 2.
Aged > 55 years and post-menopausal (stopped menstrual periods) for > 24 months.
All other women are considered to be women of child-bearing potential. Appropriate precautions will be taken in the research study to guard against inadvertent exposure of fetuses to study drugs and to inform individuals of potential risk and the need for precautions. To minimise the possibility of fetal exposure in female participants of child-bearing potential, pregnancy testing will be performed at (screening visit) to detect unsuspected pregnancy before initiation of study treatment. If negative, the individuals must also not be planning a pregnancy for the duration of the study. All efforts will be made by the investigator to ascertain that the study participants will responsibly employ a reliable method of contraception or abstinence for the duration of the drug/treatment exposure. If requested, the investigator will refer the individual to a knowledgeable counsellor or physician for contraceptive advice. Should a participant become pregnant during the study or within three months of completing treatment, she must advise the investigator who will liaise with their obstetrician.
Prohibited concomitant medications
Calcitonin, bisphosphonates, cinacalcet, teriparatide, glucocorticoids and other 1,25-dihydroxyvitamin D analogues, such as paricalcitol and doxercalciferol, are prohibited. If a participant has a medically necessary indication for the use of any of these medications, the individual will be required to withdraw from the study.
Participants will not be co-prescribed an ACEI and an ARB. Direct renin inhibitor use during the course of the study is prohibited. Individuals are permitted other antihypertensive agents that include but are not limited to: (1) thiazide diuretics; (2) calcium channel blockers; and (3) beta blockers. Local and international clinical guidelines for management of blood pressure in patients with DKD will be followed.
Run-in period
The aim of the eight-week run-in period is to optimise participants for RAAS inhibition and vitamin D levels.
Participants who have T2DM and have documented albuminuria, and meet the inclusion/exclusion criteria, will be eligible for enrolment into the RCT. If not already optimised, individuals will undergo a run-in period of eight weeks during which they will be clinically optimised for ACEI or ARB treatment (the standard of care for albuminuria) and receive ergocalciferol treatment. They will then undergo randomisation to receive calcitriol + ACEI or ARB, or continue on ACEI or ARB therapy alone. Ergocalciferol treatment is discontinued at the end of the run-in period for both intervention groups.
During the 8-week run-in period, participants will discontinue current use of any direct renin inhibitor. Those who are not treated for albuminuria will be prescribed ACEI or ARB and titrated up to the recommended or highest tolerated dose. Participants' 25-hydroxyvitamin D levels will also be measured at the start of the run-in period and, if < 30 ng/mL, they will follow the current clinical approach for vitamin D replacement which includes receiving 50,000 units of oral Vitamin D2 up to three times per week for eight weeks during the run-in period.
Individuals will be monitored for adverse effects during the run-in period. Those who tolerate ACEI or ARB and vitamin D2, if prescribed at screening, and who show adherence of > 80% with the study protocol, will then be randomised after the run-in period. Participants will be assigned to either calcitriol + ARB or ACEI group or ARB or ACEI alone group.
Throughout the run-in and study period, individuals will be treated with a goal of achieving a blood pressure target of ≤ 130/80 mmHg. Additional antihypertensive agents may be prescribed as needed. However, participants will not be prescribed a direct renin inhibitor.
- 1.
SBP ≤ 110 mmHg.
- 2.
Serum creatinine increase > 25% of the baseline level (study entry).
- 3.
Confirmed serum potassium > 6.0 mmol/L.
- 4.
Corrected serum calcium ≥ 2.62 mmol/L.
Participants who are on maximal recommended ACEI or ARB therapy and have 25-hydroxyvitamin D ≥ 30 ng/mL can be directly randomised after screening without a need for the run-in period.
Individuals will either be required to return to the study site for the outpatient visits and/or have follow-up phone calls for safety and other evaluations post randomisation at weeks 2, 4, 8, 12, 16, 20, 24 and 26.
Participant withdrawal and safety measures
- 1.
SBP ≤ 110 mmHg.
- 2.
Serum creatinine increase > 25% of the baseline level (study entry).
- 3.
Confirmed serum potassium > 6.0 mmol/L.
- 4.
Corrected serum calcium ≥ 2.80 mmol/L on one test or repeated corrected serum calcium is 2.62–2.79 mmol/L, despite dose adjustment
- 5.
Women who become pregnant during the study will be withdrawn with review to ensure safety for the mother and fetus.
Adherence to ACEI or ARB, vitamin D2 and calcitriol will be assessed by verbal assessment based on participant's reported compliance. Individuals who have consistently shown significant non-compliance/non-adherence will be evaluated by the investigator for possible withdrawal from the protocol.
Case report forms and data entry
As part of the research, participants will be asked for permission to obtain their clinical information from their medical records. Paper case report forms (CRFs) will be completed for each individual for each particular visit. Each CRF will be signed by a research investigator in order to certify that the information on the protocol is valid. The CRFs will be translated into an electronic data. All data will be double entered into a secure electronic database in preparation for data analysis. The CRF will not contain identifiable data.
Sample size calculations
A sample size of 320 individuals will be enrolled in the study. Based on the VITAL study, we estimate a treatment effect for albuminuria of d = 0.25 sd and an intraclass correlation coefficient of 75% for our current study. To achieve a power of 80% to detect a statistically significant treatment effect for a two-tailed test with α = 0.05, we calculate a minimum of 256 participants. To cater for a potential dropout of 20%, we will enrol a total of 320 individuals.
Randomisation and allocation concealment
Participants will be randomly allocated to receive either ACEI/ARB alone or ACEI/ARB + calcitriol. Allocation will be made in a 1:1 ratio via a web-based system that uses a computer-generated randomisation list with variable block sizes (2, 4 and 8). The allocations are computer generated in Stata (version 13.1) by the trial statistician and maintained in a secure database to which the trial coordinating team and investigators have no access. The randomisation sequence will be stratified by SBP (BP ≤ 130 mmHg and > 130 mmHg) and diabetes duration (≤ 5 years and > 5 years). Once a participant is eligible for randomisation, the research coordinator will log onto the randomisation website (https://www.sealedenvelope.com/) and perform the randomisation.
Statistical analysis
Demographic factors and clinical characteristics will be summarised with counts (percentages) for categorical variables, mean (standard deviation [SD]) for normally distributed continuous variables or median (interquartile [IQR] or entire range) for other continuous variables.
The primary outcome is beneficial change in the primary outcome measure (ACR [log transformed]) from baseline to 26 weeks post randomisation. Primary analysis will be assessed using repeated measures analysis of covariance using a mixed model which will take account of the within-subject variability, using ACR measurements at all post-randomisation time points and adjusting for baseline ACR level and stratification factors (SBP and diabetes duration). The adjusted mean group differences for baseline and each time point with 95% confidence intervals will be calculated. Both the crude unadjusted and adjusted estimates will be presented, but the primary inference will be based on the adjusted analysis.
Secondary outcomes will be analysed using similar methods. If the outcome is skewed, then appropriate transformations will be performed. Both the primary outcome and secondary outcomes will be analysed using the intention-to-treat principle. Findings will be considered to be statistically significant at the 5% level. Statistical analyses will be performed using Stata Special Edition Version 15.0 (StataCorp LP, College Station, TX, USA).
The impact of non-response and missing data at 26 weeks post randomisation will be examined in a sensitivity analysis. In order to avoid a loss in efficiency, missing values will be imputed using multiple imputation by chained equations. Twenty imputed datasets will be created by replacing missing values with simulated values from a set of imputation models built from all potential prognostic and the outcome variable. Additional sensitivity analysis will include per protocol analysis of the results.
The current diabetes pandemic is likely to have serious consequences for individual health, healthcare services and society. Qatar has one of the highest prevalence of T2DM in the world which is likely to translate to a significant burden of diabetes complications. DKD is a serious complication of diabetes. Albuminuria is an early marker of DKD and is treated through improved glycaemic control, blood pressure management and RAAS inhibition. RAAS inhibition, however, does not eliminate albuminuria and progression to ESRD in all patients. There is evidence that vitamin D is a negative regulator of RAAS and may provide additional benefit to ACEI/ARB treatment.
There are several specific challenges in conducting a RCT in Qatar. The population of Qatar included expatriates who speak various languages. Because of this, the informed consent was translated into several languages (English, Arabic, Hindi, Urdu, Nepali and Malayalam) and it was imperative for the research team to speak the most common languages. Another consideration is that the expatriate community is transient, with those with greatest length of stay in Qatar being more willing to participate in clinical research [46]. This may result in participant attrition. Continuous effort will be made to ensure full participation commitment and adherence and a stringent 20% dropout was included in our sample size calculation. Challenges to successful recruitment and participation in the IDEAL-2 study will inform future clinical trials in Qatar and neighbouring countries.
The impact of active vitamin D on albuminuria has reported in a meta-analysis by de Borst et al. [47]. IDEAL-2, however, differs from recent clinical trials that have examined the impact of active vitamin D treatment on albuminuria in DKD [28, 48]. Most studies have examined the impact of paricalcitol on albuminuria. In one study, calcitriol was used in those with DKD and low eGFR at a dose of up to 0.5 μg twice weekly for 16 weeks with an observed reduction in urine protein/creatinine ratio in the calcitriol group [49]. However, no optimisation of vitamin D levels or ACEI/ARB was implemented. IDEAL-2 examines a range of albuminuria, while other studies have only included those with macro-albuminuria. IDEAL-2 also aims to optimise vitamin D levels before randomisation. This will ensure that the impact of calcitriol is independent of prior vitamin D status. IDEAL-2 includes individuals on both ACEI and ARBs who will be optimised for these drugs as well as blood pressure; other studies have used a specific ACEI or ARB. The approach in IDEAL-2 ensures greater applicability of the study findings to daily clinical practice. IDEAL-2 includes longer treatment with active vitamin D (26 weeks) than previous clinical trials, essential for assessing the durability of response. It has been proposed that active vitamin D would be a useful add-on treatment to those who are refractory to salt restriction [48]. IDEAL-2 does not stipulate any salt restriction (usually a challenge for patients) or examine in detail the impact of salt intake on urinary albumin.
If the addition of calcitriol to ACEI/ARB is observed to reduce urinary albumin, this will alter current practice. The findings from the study will be disseminated through peer-reviewed publication and results presented at international meetings to healthcare professionals. Publication authorship will follow guidelines recommended by the International Committee of Medical Journal Editors (ICMJE; http://www.icmje.org/). Further dissemination will occur through the internet and social media [50]. Ultimately, findings will be incorporated into key guidelines for treatment of patients with DKD.
Trial status
The trial is currently underway. It is planned for the study to complete by 10 May 2019. The study follows protocol version (PROTOCOL_IDEAL2_ST_V2.3_8JAN2017). Any protocol amendments will be updated in ISRCTN and clinicaltrials.gov.
The IDEAL-2 study team is grateful to colleagues at Hamad Medical Corporation and Primary Health Care Corporation, Doha, Qatar for individual identification and laboratory support.
IDEAL-2 Study Team
IDEAL-2 Investigators
Department of Nephrology, Hamad Medical Corporation, Doha, Qatar:
Muhammad Asim (MA), Hassan Al-Malki (HAM), Omar Fituri (OM), Awad Rachid (AR), Abdelaziz Adel (AA), Ahmed Hamdi (AH), Awais Nauman (AN), Gamal Farghaly (GF), Mohamad Elkadi (ME).
Department of Medicine, Weill Cornell Medicine – Qatar and NY, Doha Qatar and New York, USA: Shahrad Taheri (ST).
Department of Medicine, Weill Cornell Medicine – NY, New York, USA: Phyllis August (PA), Manikkam Suthanthiran (MS).
Department of Diabetes and Qatar Metabolic Institute, Hamad Medical Corporation, Doha, Qatar: Amin Jayyousi (AJ), Buthaina Ibrahim (BI), Ibrahim Janahi (IJ), Robert Menzies (RM), Seleena Farook (SF), Salma Bashir (SB).
IDEAL-2 Research Team
Weill Cornell Medicine – Qatar (Clinical Research Core): Odette Chagoury (OC), Sopna Choudhury (SMC), Sherryl Payra (SP), Omar Omar (OO), Maria Pallayova (MP), Sahar Agouba (SA), Sally Elgazzar (SE), Hadya Elshakh (HE), Hoda Gad (HG), Samah Chalil (SC), Amany Dahir (AD).
Hamad Medical Corporation, Doha, Qatar: Hiba Tohid (HT), Subitha Chinnaiyan (SC).
The study is sponsored by Hamad Medical Corporation, Qatar. The study is funded by the Qatar National Research Fund (QNRF) through the National Priorities Research Program (NPRP) grant NPRP 4–1392–3-345. Support is also provided by the Clinical Research Core at Weill Cornell Medicine in Qatar, supported by the Biomedical Research Program funded by Qatar Foundation. There is no input from the funding or sponsor organisations into the design, conduct, analysis or reporting of the study.
Authors' contributions
Study design: ST, PA, MA, HAM, OF, MS. Study management: ST, MA, PA, HAM, OF, OC. Study conduct: MA, ST, HAM, OF, AA, AH, AN, GF, ME, AJ, BI, IJ, RM, SF, SB, OC, SMC, SP, OO, MP, SA, SE, HE, HG, SC, AD, HT. Data analysis: ST, PA, MA, OF, MS. All authors read and approved the final manuscript.
Ethics approval and consent to participate
Ethical approval for the study has been obtained from the Hamad Medical Corporation IRB (no. 16235/16), Weill Cornell Medicine – Qatar IRB (14–00039). All participants provide written informed consent.
Competing interests
The authors declare that they have no competing interests.
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary material
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Listed below are all members of the clan Shartak Merchants' Association.
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subset: commoncrawl


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TONIGHT AT 10PM- We will do what no one will do over this situation. Expose the Sheriff and his failed leadership over the Animal Control in Wilson County for many years. Taxpayers and citizens should demand change for this law enforcement officer has arrested people who save animals in that community but will not enforce laws of animal abusers or protection of animals from harm. Ten Dogs are dead and his department did not begin an investigation until a reward was offered by citizens of the county, and the interview reads the county believes that the landfill not taking dead animals is causing issues with burial of the dogs. This county is the poster child of an animal control system so political and managed by people who do not truly care about the animals but their career. If Wilson can have a sheriff that will not managed animal control as his job duties require. BB&T and other companies should be aware of the law enforcement problem in Wilson and look elsewhere to have a presence. This county treats animals bad and ten dogs are dead. If someone will kill a dog, they will kill humans.
Via @WRAL: Wilson County residents on edge after dead dogs found in trash bags https://t.co/rKejj27YOm
— Wise&Whitehall (@DogsWayneNC) April 3, 2018
Please leave a response about changes needed in Wilson County
Reading the story about the ten dead dogs in Wilson County, the WRAL news story leaves some very important facts about this situation as they accept the Animal Control story of being on top of the investigation and giving the innocent reason that people are not able to bury their dogs at the landfill.


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Monday, July 16, 2007
Off we go!!!
Tomorrow P-Tizzle and I will be off to the La Leche League International Conference in Chicago, IL!
I am so excited about all the fabulous speakers, the unique and interesting exhibits and hanging out with so many other "lactation nerds", gentle parents and authors of all the books I like BUT a little worried as to how I will keep a 13 month old entertained during sessions for 5 days! Pray for me, mothers, pray.
So, if you see a frazzled, tired-looking mother with dreadlocks and a wild-eyed, curly-haired little tornado say "hello"! And maybe offer me some chocolate or an adult beverage.....
I'd like to know if any Mocha Milk readers will be at the conference? Please leave a comment and let me know if I should look out for you. We can sit together at a luncheon!
It's not too late to register. To find out more information about the conference visit La Leche League's newly redesigned website.
3 comments:
hi mickey... it was great to meet you and i hope to make it to the cappa conference in sc. i found out there is a mochmom's chapter in greenville. please be honest and tell me if it is socially inappropriate for me to join or visit??
- July 24, 2007 at 4:55 PM
hi mickey! it was great to meet you, and i hope to run into you again at some boobnerd event. i'm also hoping to visit the farm in the fall, so perhaps we could get together then. i will try for cappa in sc too... ps. honestly-- do you think it would be socially awkward or inappropriate for me to join mochamoms/go to a local meeting?? firstname.lastname@example.com
- July 24, 2007 at 5:29 PM
- Elizabeth F. said...
You lucky dog! I wish I could have gone to the conference. I am LLL Leader!
Anyway, I'm having a Give-Away at my blog for Breastfeeding advocacy Note Cards. Come on by and enter before Friday.
- July 25, 2007 at 1:28 PM


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The Worth Of Music In My Life
Hip-hop is not just about music. Many cultures have strong traditions of solo performance (through which one singer or instrumentalist performs), resembling in Indian classical music, and within the Western artwork-music tradition. The musical theater of the folks took a number of kinds: the bagatelliste drama, the commedia delL'arte, and the Singspiel. In the identical period there were monster performances in England with over four,000 individuals, half of whom had been singers.
This distinction amongst singers, gamers, and mere listeners is additional subdivided into two categories : familiar music-enjoying," represented up to now by the regular efficiency of music by town musicians, performances at church festivals, court docket music, music performed at desk, and so on., and the trendy performance," which presupposes thorough examine of the music to be played, by orchestras and en sembles.
In well-liked music and traditional music, the act of composing, which is usually referred to as songwriting, could involve the creation of a primary define of the music, known as the lead sheet , which sets out the melody , lyrics and chord progression In classical music, the composer sometimes orchestrates his or her personal compositions, however in musical theatre and in pop music, songwriters …


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Art Throughout the Airwaves with Papadosio
The moment Papadosio transcends the stage, an electric vibe radiates throughout the venue. It's as if everyone shifts into a mellow bob of a dance, all as one. Their joyful stage presence and funky beats allow their fans to dance carefree. No wonder so many people crowd around in anticipation for the band to begin.
After becoming obsessed with their song "You as Yourself", I am psyched when Papadosio graciously accepts an interview. Walking backstage into a room of the smiling faces of Sam Brouse, Billy Brouse, and Mike Healy, showed I was about to interview some cool, down-to-Earth individuals.
How did you guys gather as a band?
Sam Brouse: Well, we all met in Athens, Ohio, at this gathering party every Tuesday night called Open Jam. It's different from open mic. Open mic implies that there is usually one guy with an acoustic guitar, singing. It was started by a bunch of music instructors from OU campus/Hocking College. So I got there with my guitar and asked, "Can I play with you guys?"
I didn't know how to play at all. They showed me the ropes. We were all younger initiates playing with these really skilled musicians. We started to do it about every week. It was probably a collective of 12-20 dudes a night. It was awesome.
Mike Healy: You came and we were all like, "Who's this guy?" And then that night we jammed and we were like, "He's awesome; I want to play with him so bad." It was love at first strum.
Was it complete improv?
Sam: It was all improv. Every once in a while people would revert to jazz standards like "Watermelon Man" or "Chameleon", pretty much once a night- all those classic songs that everyone knows. Every once in a while we would do the craziest stuff. And then we were like, "Man this would be cool as a band." So we got together.
It says on your Facebook page that your mission is to combine eclectic musical traditions with modern electronica, to stir the heart, and fuel the mind. Can you elaborate on that?
Mike: I feel like from the very start there has always been this whole element of combining the organic rock and roll music that we were all so influenced by growing up, that we wanted to combine it with a new digital electronic sound. The game plan was meshing these two worlds together, creating a new, different kind of sound, most of our songs have several different kinds of elements that reach from different styles of music. We are really trying to fuel people with positive vibes about humanity, the Earth, and the environment. And at the same time bringing people together, raising that vibration of love in every room that we play. Hopefully, people can take away those vibes from our music.


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Dating but nothing to talk about
However the real challenge here maybe to convince your partner to join a new class with you. Maybe you are struggling with a relationship of your own or just plain paranoid you might one day end up where some of these disappointed tweeters have landed. If you perpetually bring up what trouble the kids got in school and how the mortgage is overdue, then your partner will find it preferable to keep quiet rather than engage in stressful discussions. So shake yourself out of this complacent mode and make an effort into knowing what your partner is doing, thinking or planning these days. Leave a comment and share your advice. It can help you live your day more mindfully—make you more aware of your actions and choices, and more grateful for your blessings. If you cannot resolve the issues on your own, discuss matters with a trusted friend or a counselor. She tells couples to practice the five A's: You may have booked the baby-sitter, dolled yourself up and manage to get a table at the swanky restaurant, but when you sit down, you find yourselves either painfully quiet or coming up with stale questions to each other. In fact, I often felt as if huge portions of my brain, my personality, and my professional life were on hold. It may not always be necessary to come up with a compliment — indeed fake or insecure praise may seem unnatural and forced and do more harm than good. Rather focus on what is comfortable and interesting.


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|Forum for former BBC staff
>> Notices, obituaries and tributes >> John Timpson
Message started by Forum Admin on Nov 19th, 2005, 4:08pm
Title: John Timpson
Post by Forum Admin on Nov 19th, 2005, 4:08pm
One of the big names in the history of radio, John Timpson, has died. He was a distinguished reporter in newspapers and television, but is best remembered for his 16 years on the Today programme.
He shared the main presenting duties first with Jack de Manio, then Robert Robinson and finally with Brian Redhead.
This is the BBC News Online report of John Timpson's death.
Title: Re: John Timpson
Post by Alan_Ashton on Nov 20th, 2005, 10:45am
I had the privilege of working closely with John Timpson when, after a brief spell in television, he returned to Today in 1978 and began his successful partnership with Brian Redhead.
he was always the lighter of the two - the man with the velvet voice one producer called him - but woe betide any duty editor or producer who tried to give Brian all the serious interviews.
He never, like Brian, enjoyed the world of politicians, trade union leaders etc., but that didn't mean he couldn't handle them. After the celebrated run in with Norman Tebbitt, he nursed his post programme whisky (in a paper cup) and expressed his satisfaction that Tebbitt had referred to him as "Mr. Timpson". "None of this first name familiarity with me Badger "(my nickname).
He could be a pain at party conferences and trips abroad as he couldn't wait to get back to his wife Pat, his family and his home in Chorleywood.
He chided me for saving money on air fares to a summit in Ottawa as it gave us two extra "free" days in that lovely city!
On his retirement from the BBC, he kept up his talks to WIs and Townswomen's Guilds (ladies of a certain age adored him) and his book writing, mainly about English heritage.
He promptly moved to his holiday home at Wellingham in Norfolk where he had cut his journalistic teeth as a cub reporter. He loved the area and after a few years moved to a larger house in another village - Weasenham, half way between Swaffham and Fakenham.
It was there that I last saw him and Pat about 18 months ago.
He never seemed to hanker after the bright lights or the celebrity life style. As we nursed a post lunch drink, looking over a village green with a duck pond and a pub within walking distance, I suggested it was idyllic.
"Blessed ducks - muck up the garden", he replied.
Title: Re: John Timpson
Post by Forum Admin on Nov 21st, 2005, 8:14am
This is taken from The Guardian:
John Timpson
Broadcaster whose unflappable style brought a reliable calm to the Today programme
by Dennis Barker
Monday November 21, 2005
John Timpson, who has died aged 77, was a radio and television interviewer and presenter of the old school. Precise but good-natured, he was not in thrall to metropolitan culture, preferring to live on the refreshing plains of Norfolk. He always treated those he questioned on the Radio 4 Today programme - where he was co-presenter from 1970 to 1976, and from 1978 to 1986 - with firmness, but also with respect. He had a liking for the humorous aside.
Whether his agreeable style, or the more aggressive approach of John Humphrys and James Naughtie, was best calculated to reveal truths is debateable. What is incontestable is that Timpson was a thoroughly unflappable professional, who was not afraid of getting up at 3am to face any challenge. Though he was the emollient partner of several more angular personalities on Today, including Robert Robinson and Brian Redhead, he was originally brought on board to give the programme a harder, more newsy flavour than Jack de Manio, who had been doing the job for 11 years. (Timpson found de Manio "unpredictable" - as when he gave great offence by pronouncing the word for the river Niger as if it were the river black person.)
Timpson became an expert at providing early-morning stability to Today, which then had 4 million listeners, mostly bathing, showering, shaving or trying to get their breakfasts. He always joked that he had got softer as the years went by - he secretly preferred the lighter stories - and that Robinson had got harder in his news sense. He claimed sardonically that he regarded curtailing some of Redhead's willingness to "talk all day" as his duty to the British nation.
One of his great knacks was to introduce even quite serious items in a way likely to keep people cheerful over their breakfasts. When introducing a story about a report by David Widdicombe, QC, on local government, he explained the story and then asked a potential critic of the report: "Is Widdicombe fair?" He could be jokey in a way that only the pompous could take amiss.
Timpson's 18-month break from Today in 1976 was the result of his flirtation with television, when he presented Tonight on BBC1. Christopher Capron, its director, had worked with Timpson on Today in the early 1970s and had been impressed by the quickness of mind behind the plain-and-simple-man image. His impressive calm was another television asset; it had been noticed on Today that while others in the studio lost their tempers, or at least their cool, the tall and beetle-browed Timpson always carried on as if nothing was happening. A certain caution underpinned his calm; he had, after all, chosen to pass up the opportunity of high freelance fees in favour of the security of remaining a BBC staff member.
For a time Timpson even did Today and Tonight together, arriving at the BBC at 5.15am and working until after midnight. But when he had to decide between the two, it was the television job that he left, protesting that it had never been his medium. Self-flaunting display was not his forte. "I suppose I shall have to have my hair cut and buy a jacket that matches my trousers," he had said as he took the television job; by the end, he was relieved at not having to bother with such considerations.
Timpson's beginnings were mostly in the provinces, though he was born in Kenton, north London, the son of a bank manager. He went to Merchant Taylors' school but left in 1945, aged 16, to become a reporter on the Wembley News, interrupting this to do his national service in the Royal Army Service Corps. He returned to Wembley from 1949 to 1951 before joining the Eastern Daily Press in Norwich.
In 1959, he joined the BBC news staff as court correspondent, and covered royal events in Ethiopia and Australia, as well as at home. Five years later, he became a television presenter on BBC2 and was then recruited to Today.
Chairing the Radio 4 Any Questions programme from 1984 to 1987, Timpson handled even heavyweight political personalities with panache. Later, he switched allegiances and presented Timpson's Country Churches for ITV, from 1995 to 1998. He won the Sony Golden Award for outstanding services to radio in 1986, and was awarded the OBE the following year.
In retirement, he was the exact opposite of the archetypal media figure who cannot rest unless he is appearing personally before a public. He and his wife, Muriel, moved permanently into the cottage that had been their weekend home for years, the Ark, near King's Lynn, on the north Norfolk coast.
For long the secretary of the local parochial church council, Timpson had already published his autobiography, Today and Yesterday (1976), The Lighter Side of Today (1983), The Early Morning Book (1986) and Timpson's England - A Look Beyond the Obvious (1987). He now launched into publishing a series of books with more ease and success than many former broadcasters.
His work reflected his interest in the countryside and non-metropolitan life generally: Paper Trail, a novel about the mishaps of a young provincial reporter (1989), Timpson's Towns (1989), Timpson's Travels in East Anglia (1990), Sound Track, a novel, and Timpson's English Eccentrics (both 1991), Little Trains of Britain and Timpson's English Villages (both 1992), Timpson's Other England (1993), Timpson's Timepaths (1994), Timpson's English Country Inns (1995), Timpson's Book of Days (1996), Timpson's Adaptables (1997), Timpson's Country Churches (1998), Timpson's Leylines (2000), Timpson's Norfolk Notebook (2001) and Timpson on the Verge (2002).
He is survived by Muriel, whom he married in 1951, and one son. Another son, Nick, died five weeks ago.
Sue MacGregor writes: My very first morning presenting the Today programme, in the autumn of 1984, was made a good deal less frightening for me because my on-air partner was John Timpson. I'm not sure what he really thought of this female cuckoo in the then very masculine nest of Today, but he steered me through the complications of the running order with great kindness: at first, even getting the time checks right is much more difficult than you might suppose.
John was a meticulous broadcaster, who never forgot that listening to live current affairs broadcasts is not at all the same as reading a morning newspaper, so you'd better make everything as clear as you can. Like his famous on-air partner Brian Redhead, he had no time for mumblers. Like Brian, he came into broadcasting from print journalism, but in other respects they were very different people. John was pretty bored by serious politics, though he could do a tough political interview, and thought Today should have sufficient room for humour. His "ho ho" quips, invented to fill the little gaps before the time-checks in the days of the so-called regional opt-outs, quickly became a favourite part of the programme.
I still remember John's deadpan comment after a feature on the run-up to one of the latest Eurovision Song Contests of the early 1980s. "The first time I watched it, the lyrics of our entry went along the lines of 'Singing high, high, high; singing low, low, low', and as far as I can tell the standard of lyrics has declined every since." Slight pause - on to next item. He could judge that sort of thing perfectly, making the listeners feel he was on their side, and that being a fan of Today was like belonging to a rather good club.
· John Harry Robert Timpson, broadcaster and writer, born July 2 1928; died November 19 2005
Title: Re: John Timpson
Post by Forum Admin on Nov 21st, 2005, 8:17am
This is taken from The Times:
John Timpson
July 2, 1928 - November 19, 2005
Former presenter of the Today programme and Any Questions who was renowned for his professionalism and cheery humour
AS A broadcaster, John Timpson was a true professional, and for the aficionados of Radio 4, one of the first voices they would hear upon waking up each morning. He was one of a generation of radio journalists who rose through the ranks in a career that spanned three decades. It varied from news reporting, through programme presentation mainly a memorable era as co-presenter of the popular early-morning news magazine Today on Radio 4, to chairmanship of the long-running Any Questions programme.
His period as co-presenter of the Today programme, from 1970 to 1986, was perhaps his apogee. It was certainly the role that made his voice a household one. He had a style that was relaxed and exhibited a droll and wry sense of wit. As an interviewer he was always polite and, demonstrating the mark of the professional that he was, never allowed his own politics or views to intrude.
He was awarded a Sony Gold Award for outstanding services to radio in 1986. Thereafter he largely devoted himself to the medium of print, in which he charted in various volumes the history and nuances of English rural life. But whether it be radio or the written word, Timpson was always renowned for his one-liner quips, avuncular disposition, humanity and most of all his bright sense of humour.
John Harry Robert Timpson was born at Harrow, Middlesex, and educated at Merchant Taylors School. His career in journalism began on the Wembley News in 1945, but was interrupted by National Service in the Army. In 1951 he left suburban London to enjoy the open spaces and eccentricities of East Anglia as a district reporter on the Eastern Daily Press and one of its weekly associates, where he remained for the next eight years.
In 1959 Timpson returned to London and joined the BBC news staff, working firstly as a radio reporter. As deputy to the legendary BBC Court Correspondent Godfrey Talbot from 1962 to 1967, he covered many royal engagements, including tours of Australia and Ethiopia.
For a couple of years in the 1960s, in the wake of the introduction of a new breed of studio anchormen, he moved to television as presenter of the Newsroom programme on BBC Two. Timpsons best achievements, however, were on radio. In 1970 he became the first co-presenter of the Today programme with Jack de Manio, for whom he had occasionally deputised.
The eccentric and rather irascible de Manio felt that the character of the programme changed with the introduction of two presenters who, he believed, were in danger of talking to each other rather than the listener. He left and Timpson, who did not hold the same view, was joined for a time by another highly professional performer, the voluble Robert Robinson.
To some extent de Manios fears were proved right. We threw in jokes to fill in the gaps. Timpson once remarked, but the badinage did not adversely affect the programmes popularity and there was more of it quips about all manner of things from roadworks on the M6 to cricket, and nostalgia about things such as seaside piers.
Timpson was later joined by Brian Redhead for what became a popular and longstanding partnership, interrupted only by Timpsons departure. He had returned to television in the 1970s as presenter of the BBC One Tonight programme, but after two years was back in his familiar seat on Today.
In 1984 he had also taken on the chairmanship of the long-running radio programme Any Questions. By 1986, however, Timpson had become tired of the necessary early rising for the Today programme and, to the envy of many colleagues, he retired early to a 17th-century cottage in north Norfolk, an area of England for which he had always retained a deep affection. He continued to travel the country with the Any Questions team, but eventually he gave this up too.
He was appointed OBE in 1987, the year after he received a gold award for outstanding services to radio. Timpsons radio experiences had provided material for several books: Today and Yesterday (1976), The Lighter Side of Today (1983) and The Early Morning Book (1986).
Now freed of the inhibitions of regular broadcasting he wrote a series of travel books Timpsons England (1987), Timpsons Towns (1989), in which he looked at the oddities and peculiarities of the English scene, and, appropriately, Timpsons Travels in East Anglia (1990). He also wrote a requiem for the red telephone kiosk, and his first novel, Paper Trail, an amusing distillation of his youthful experiences as a reporter in rural Norfolk, was published in 1989. Subsequent books included Timpsons English Villages (1992), Timpsons Other England (1993), Timpsons English Country Inns (1995) and Timpson on the Verge (2002).
John Timpson can truly be said to have travelled full circle: in his semi-retirement he wrote a regular column for his old paper and was church warden of his village church.
He had been married since 1951 to Patricia, who survives him, as does their son. A second son, Nick, died suddenly at 42, five weeks ago.
John Timpson, OBE, broadcaster, was born on July 2, 1928. He died on November 19, 2005, aged 77.
Title: Re: John Timpson
Post by Forum Admin on Nov 21st, 2005, 8:21am
This is taken from The Independent:
John Timpson
'Today' programme presenter who established a formidable partnership with Brian Redhead
Published: 21 November 2005
John Harry Robert Timpson, writer and broadcaster: born 2 July 1928; reporter, Wembley News 1945-46, 1949-51; reporter, Eastern Daily Press 1951-59; member, BBC News Staff 1959-87, deputy court correspondent 1962-67, presenter, Newsroom 1968-70, Today 1970-76, 1978-86, Tonight 1976-78, Any Questions 1984-87; OBE 1987; presenter, Timpson's Country Churches, ITV 1995-98; married 1951 Patricia Whale (one son, and one son deceased); died King's Lynn, Norfolk 19 November 2005.
The Today programme on BBC Radio 4 has been a broadcasting institution almost from the time it was launched in the 1950s on the old Home Service; but since then it has gone through several changes of personality. In the early days, with the ebulliently endearing Jack de Manio as ringmaster, its tone was gentle and quixotic as it tried to ease listeners tenderly into the day ahead, with little to raise the blood pressure as they dipped their soldiers into a boiled egg.
Nowadays it is the very opposite, as the irascible John Humphrys and Jim Naughtie pick fights with anyone who dares sit across the studio table from them, hoping to make us choke on our porridge. John Timpson's tenure, from 1970 to 1986 with a short gap in the middle, marked the transitional period between those two contrasting styles of current affairs radio.
During much of that time he shared presentation duties with Brian Redhead, and they made a splendid combination. Timpson, with a deep, rich voice, perfect for radio, was the natural heir to de Manio, though slightly less eccentric and better at telling the time. He shared his predecessor's gentle manner and his partiality for the quirky and the ridiculous; but as a former reporter he took a rather more rigorous approach to the news.
Redhead, the former editor of the Manchester Evening News, was equally loved by listeners but was capable of introducing a sharp tone into political interviews, laying the groundwork for his terrier-like successors. As a pair, he and Timpson were the classic hard cop, soft cop combination, as compared to the hard cop, hard cop regime that rules in these more combative times.
Their different personalities meant that relations between them were not always cordial. Timpson once described Redhead as "the walking image of every garden gnome you'd ever seen" and revealed that they often quarrelled "like two spoilt kids", even sometimes on air.
Timpson became a journalist in 1945 when, at 17, he joined his hometown paper, the Wembley News, straight from Merchant Taylors' School. He left after a year to do his National Service in the Army but rejoined the paper afterwards and stayed there until 1951. That was a critical year in his life, for it was then that he married Patricia Whale and moved to Norfolk to join the Dereham & Fakenham Times, soon switching to the Eastern Daily Press.
He did not take instantly to Norfolk. "To a born-and-bred suburbanite, on a wet Sunday in January in the early 1950s, it looked like the end of the civilised world," he wrote. Yet he soon warmed to it and his love of East Anglia, and of rural life in general, was reflected in several of the books he would later write.
Indeed, it was with some reluctance that he relocated to London in 1959 to begin his broadcasting career with the BBC, as a news reporter for both radio and television. He was appointed deputy court correspondent in 1962 and made several tours abroad with the Queen and the Duke of Edinburgh. In 1968 his easy, confident manner persuaded the BBC that he would make a natural presenter and he did a stint on Newsroom, one of several short-lived attempts by the controllers of BBC2 to produce a news magazine before they hit on the successful Newsnight formula a decade later.
In 1970 he was poached by Radio 4 to present Today. The immensely popular de Manio was a hard act to follow, but Timpson and Redhead very soon gained the loyalty of the programme's two and a half million regular listeners. They became household names - so much so that after six years Timpson was lured back to television to present Tonight. This was not Cliff Michelmore's legendary early evening programme of the Sixties, but a less successful late evening version whose other presenters included Sue Lawley and Donald McCormick.
After two years, his BBC bosses decided that he was more suited by radio than television. His slightly moon-faced appearance was seen as a drawback at a time when chiselled film-star features were becoming a must for on-screen newsreaders and current-affairs presenters. So he went back to the invisibility of Today, this time for an eight-year stint. And from 1984 he combined this with taking the chair of Radio 4's weekly discussion programme, Any Questions.
On leaving Today in 1986 Timpson was presented with a Sony Gold Award for outstanding services to radio, and the following year he was appointed OBE. From then on, he devoted much of his time to writing books. He had already produced an autobiography Today and Yesterday (1976) and an account of his adventures in radio, The Lighter Side of Today (1983), but from 1987 he began a popular series of travelogues about England, beginning in 1987 with Timpson's England: a look beyond the obvious.
For a time he wrote a column in the Daily Mail and in 1995 returned to television, presenting an ITV series called Timpson's Country Churches, which spawned one of his most popular books. His last, published in 2002, was Timpson on the Verge, about road signs in Norfolk villages.
In his later years he took an active part in the life of his own Norfolk village, Weasenham St Peter, near King's Lynn, as secretary of the parochial church council. In an interview last year he said he loved the peace and quiet and the absence of tourists - deterred, as he thought, by Noël Coward's laconic description of the county as "very flat". He said he still listened to part of the Today programme, but then switched over to "the real world" of Radio Norfolk.
Michael Leapman
Title: Re: John Timpson
Post by Forum Admin on Nov 21st, 2005, 8:25am
This is taken from the Daily Telegraph:
John Timpson
(Filed: 21/11/2005)
John Timpson, who died on Saturday aged 77, was a popular presenter on Radio 4's early morning news and current affairs programme Today from 1970 to 1986.
His crisp but cheerful and relaxed voice and his dry sense of humour became an integral part of the breakfast routine in millions of households. One-liners such as "Insulation - Britain lags behind" or "Crash course for learner drivers" were an intrinsic part of his style and humour, as was his habit of punctuating jokes with a basso "ho ho".
He was also noted for the politeness of his interviews, which earned him a reputation of being "one of the nicest people on the BBC". His instinct for journalistic detachment also made him careful to display impartiality when dealing with political issues.
At times he felt obliged to "play the devil's advocate, putting forward the other side of the argument", but he said: "I hope I have never revealed the way I vote."
His voice was variously described as avuncular, fruity or reminiscent of dark brown chocolate, but overall perfectly matched the dawn. Sean Day-Lewis observed in The Sunday Telegraph that it suggested "a man who has had to leave his bed quickly because of some emergency, dishevelled but determined, seeing things through with a rueful sense of humour".
This impression was in many respects true of the daily routine. A microphone deadline of 6.30am meant waking up at around 4am, for which Timpson relied on two alarm clocks as well as an early morning call. He often slept in the Langham Hotel, opposite the BBC, on the night before he was to present a Today programme. He would get to work at 4.30am to read the newspapers before attending a 5.30am briefing and typing his script.
Libby Purves observed that beneath his cheerful manner he sometimes had "cross, grumpy cantankerous mornings". "But," she went on, "when, in the old days, I would be on the point of braining John with a waste-paper basket, some spontaneous but beautifully paced Timpson joke would disarm me."
He was, as she admitted, "a total professional: a straight, polite interviewer whose politics are publicly neutral. Above all he is a purveyor of beautifully crafted jokes."
He had the reputation of being unflappable. In fact Timpson's relaxed style belied his skill and quickness of mind as he tackled what was essentially a complicated craft job. Libby Purves pointed out that his skill lay in managing the requirements to "hit fixed time points with precision, cut off garrulous ministers in time to get Thought for the Day on [and] think of quick one-liners to change the pace without taking more than eight seconds over them".
A large affable man, over six feet tall with kind brown eyes, Timpson was described by John Gaskell in The Sunday Telegraph as "well suited to the role of an agreeably indulgent uncle".
When he retired from Today on Christmas Eve 1986 he had helped to present nearly 3,000 editions and his co-presenters over the years included Jack de Manio, Robert Robinson, and Brian Redhead. He received the Sony Gold Award for outstanding services to radio and the following year, 1987, he was appointed OBE for outstanding services to broadcasting.
Yet the qualities which made Today his forte did not serve him well on television. In 1976 he attempted to become a television presenter on the BBC2 current affairs programme Tonight, but left after 18 months to return to Today.
Critics variously described some of his interviews as "lightweight" and "rather unctuous" and Timpson himself later commented: "Basically, I didn't look as good on TV as I sound on radio."
He was chairman of Radio 4's Any Questions? for three years from 1984 to 1987 but, although in control, "never seemed at ease," according The Sunday Telegraph.
His long introductions were said to leave some guests shaking with rage at their inappropriateness and his announcement: "That, ladies and gentlemen, is your panel," displayed what many felt a remoteness from the Any Questions? audience. It may simply have been that years presenting Today had created too distinctive a stamp of personality for the programme.
John Harry Robert Timpson was born at Kenton, Middlesex, on July 2 1928, the son of a bank manager. He was educated at Merchant Taylors' School but left at 16 to become a cub reporter with the Wembley News.
His career was interrupted by National Service with the Royal Army Service Corps from 1946 to 1949, after which he returned to the Wembley News until 1951, when he joined the Eastern Daily Press.
In 1959 he joined the BBC as a radio and television reporter on general assignments both at home and abroad and from 1962 to 1967 was the BBC Deputy Court Correspondent reporting on the Australian, Ethiopian and other Royal tours.
He then switched to the world of international politics, reporting Harold Wilson's Tiger talks with Ian Smith; the coup in Greece; Rhodesia's independence as Zimbabwe; and three American presidential elections.
He was a newscaster on BBC2 from 1968 to 1970, before joining the Today programme as a junior presenter in 1970 with Jack de Manio. Timpson belonged to a generation of radio journalists who rose through the ranks and emerged only in middle age as front-rank presenters. Unlike many of his contemporaries, he did not become a freelance, which offered more pay, but remained on the staff of the BBC.
He described himself as a man wondrously lucky to have had the career he enjoyed. He was also relieved that his "one big howler" was not dug up. That was when he described the marathon walker Barbara Moore as "climbing the steps of Marble Arch". There are no steps to Marble Arch: Timpson, who was on location and had lost her in the crowd, was desperately ad libbing.
After retirement from broadcasting he moved to his country cottage in Norfolk, and continued to write a column for the Eastern Daily Press. He also compiled an anecdotal book about places of interest, Timpson's England - A Look Beyond The Obvious (1987), and many others (including volumes on inns, country churches, trains, towns, villages, eccentrics and - oddest of all - ley lines) in a similar vein. He also published an autobiography, Today and Yesterday (1976); The Lighter Side of Today (1983), and The Early Morning Book (1986).
For many years he owned a four-berth cabin cruiser in which he and his family would escape to "somewhere in East Anglia".
He married, in 1951, Patricia Whale; they had two sons, one of whom died earlier this year.
Title: Re: John Timpson
Post by Forum Admin on Dec 14th, 2005, 9:38am
This letter recalling John appeared in The Guardian, December 13, 2005:
from Marshall Stewart
Recruiting John Timpson (obituary, November 21) to form the first two-man presenter team for BBC Radio 4's Today programme was a key part of restructuring what was already an institution. In 1970, Today was a world away from its subsequent role as the network's news and current affairs flagship. Before taking over as editor, I visited the studio. The first edition completed by 7.45am, the team left the studio and decamped to a dining room where a waitress produced breakfast on silver trays. When I inquired about the impending second edition, I was told: "No need to worry. We record the first edition and play it again after the eight o'clock news."
John came with a substantial track record as a BBC television and radio reporter, plus BBC2 experience as a presenter. He negotiated the tricky process of establishing himself alongside the legendary Jack de Manio with much patience and some humour, before forging more straightforward partnerships with Robert Robinson and Brian Redhead.
Much has been made of John's predilection for light-hearted material. Yet I remember being alongside him on the roof of Broadcasting House, Belfast, as he introduced Today against the background of small arms fire during the period of internment, when his real strengths as a newsman showed through. True, later in the programme, he interviewed a Belfast comedian about the art of telling sectarian jokes across the divide, but that was confirmation of his belief, as a listener's broadcaster, that life - and Today - is about light as well as shade.
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