the prevalence of type 2 diabetes mellitus ( t2 dm ) is rapidly increasing worldwide in parallel with the current obesity epidemic . in 2010 the global prevalence of type 2 diabetes was estimated at 8.3% of the adult population and 23% of patients with morbid obesity have type 2 diabetes . these data are projected to increase and prevalence of diabetes is expected to reach 9.9% by 2030 . conventional medical treatment of type 2 diabetes may achieve only partial glycemic control and reduction of cardiovascular risk , especially if associated with obesity . although initially developed solely as a weight reduction therapy , bariatric surgery has been reported to cure and improve type 2 diabetes and to reduce rates of cardiovascular disease and death [ 36 ] . a meta - analysis of studies   on various bariatric procedures involving patients with type 2 diabetes showed an overall rate of remission of hyperglycemia of 78% among the various procedures . remission occurred in approximately half of patients who underwent laparoscopic adjustable gastric banding ( lagb ) , 80% of those who underwent roux - en - y gastric bypass , and 95% of those who underwent biliopancreatic diversion ( bpd ) . data regarding diabetes remission following laparoscopic sleeve gastrectomy ( lsg ) are extremely variable amongst authors . in a meta - analysis   that analyzed 27 studies and 673 patients , diabetes remission was reported in 66.2% of cases and improvement was reported in 26.9% of cases . in our previous studies diabetes remitted in 80% of patients [ 9 , 10 ] , results that have been predominantly confirmed by a recently published meta - analysis by yu et al . . showed a direct correlation between weight loss and the remission of diabetes following various surgical procedures . bariatric literature usually presents results in terms of rate of diabetes cure or remission , usually defined as the normalization of glucose levels and glycated hemoglobin ( a1c ) in the absence of active antidiabetic therapy . in analogy to the oncologic literature , where cure is defined as complete remission of cancer of sufficient duration that the future risk of recurrence is felt to be very low , experts agreed that it may make sense , on a practical ground , to consider prolonged ( arbitrarily 5 years ) remission of diabetes essentially equivalent to cure . experts agreed that it may make sense , on a practical ground , to consider prolonged ( arbitrarily 5-year ) remission of diabetes essentially equivalent to cure . in this context partial remission  is a1c < 6.5% and fasting glucose between 100 and 125  mg / dl for a period of at least 1 year 's duration in the absence of active pharmacologic therapy . complete remission  is a return to  normal  values of glucose metabolism ( a1c < 6% , fasting glucose < 100  mg / dl ) for at least 1 year 's duration . oral glucose tolerance tests ( ogtt ) are difficult to interpret both because of the modified glucose kinetics after surgery and because of the lack of reference data which define a another question that arises from bariatric literature is the correct diagnosis of diabetes , both before and after surgery . diagnosis of diabetes should be always performed according to ada ( american diabetes association ) guidelines   which , besides other criteria , take into account a detection of random glycemia over 200  mg / dl during the day . bariatric surgeons usually assess the presence of type 2 diabetes mellitus before surgery on the basis of the existing oral treatment regimen of patients ( e.g. , metformin treatment ) ; following surgery they often define diabetes remission on the basis of fasting glycemia values , without a specific consideration to postprandial glycemic peaks . it is now widely known that acute fluctuations of glucose around a mean value over a daily period of intermittent hyperglycemia may play an important role in the development of cardiovascular disease in type 2 diabetic patients [ 15 , 16 ] . fasting plasma glucose is usually normalized in postbariatric patients , while little is known about their glucose profiles throughout the day , especially immediately after meals , and about how this variability can affect the development of future micro- and macrovascular complications . in literature , only few cases undergoing gastric bypass have been assessed through continuous glucose monitoring ( cgm ) . these cases show early hyperglycemic peaks after either a meal test or a glucose load , followed by a rapid fall to very low glycemic levels , with postprandial symptoms as seen in dumping syndrome . however , these authors have focused their attention only on the use of cgm in relation to hypoglycemia resulting from the operation [ 17 , 18 ] . the aim of this study was to evaluate glucose variability assessed by cgm in obese type 2 diabetic patients that underwent lsg , who were defined as cured of diabetic disease according to international criteria , which consist in fasting glycemia < 100  mg / dl and a1c < 6% in absence of hypoglycemic therapy . a total of 20 morbidly obese patients were enrolled 3 years following lsg to perform cgm to evaluate glucose plasma variability and ogtt for glucose tolerance evaluation . patients were recruited at the centre of diabetes and metabolic diseases of sapienza university in rome . all the patients were diabetics before surgery with t2 dm diagnosed according to american diabetes association guidelines . the primary clinical outcome was evaluation of real diabetes remission after lsg by assessing glucose variability by cgm and glucose tolerance by ogtt . the follow - up lasted at least 42 months consisting in clinical examinations with anthropometric measurements and routine laboratory tests with glucose metabolism assessment every 3 months . diabetes remission after lsg was then defined as a fasting glucose level of less than 100  mg / dl and an a1c level of less than 6% in absence of treatment . the results were then related with retrospectively collected data , referred to each patient before surgery in order to look for prognostic factors of the diabetes resolution obtained by lsg , including anthropometric parameters , duration of diabetes , age , bmi , insulin use , and fasting c - peptide as marker of insulin secreting ability . the following parameters were recorded at baseline and three years after surgery : age , gender , body mass index ( bmi ) , and systolic and diastolic pressure.ongoing drug treatments.fasting blood levels of glucose , a1c , total and hdl cholesterol , and triglycerides . age , gender , body mass index ( bmi ) , and systolic and diastolic pressure . ongoing drug treatments . fasting blood levels of glucose , a1c , total and hdl cholesterol , and triglycerides . standing height , weight , and waist circumference were measured with subjects wearing light clothing . obesity was estimated by means of bmi [ weight ( kg ) divided by height  height ( m ) ] . blood pressure ( mmhg ) was measured after five minutes of rest with the patient sitting in the upright position . three measurements were obtained , and the average of the second and third ones was recorded and used in the analysis . patients underwent fasting blood sampling to assess blood glucose , a1c , total cholesterol , high - density lipoprotein cholesterol ( hdl ) , and triglycerides , by standard laboratory methods carried out by our center . the surgical operation was applied as the previously described technique   in which five trocars are needed . the division of the gastric greater curvature vascular supply , starting at 6  cm from the pylorus and proceeding upwards until the angle of his , is carried out with radiofrequency ( harmonic scalpel , ethicon endosurgery ) or with caiman 5  mm vessel sealing device ( aesculap ) . the gastric resection was performed using a linear stapler ( echelon flex endopath stapler , ethicon endosurgery ) , with two sequential green load firings for the antrum , followed by three or four sequential gold loads for the remaining gastric corpus and fundus . the stapler is applied alongside a 42  fr calibrating bougie strictly positioned against the lesser curve , to obtain an 80100  ml gastric volume . the last shot of stapling was fired at least 1  cm distal to the esophagogastric junction . reinforcement of the staple lines was performed with bioabsorbable strips ( gore seamguard bioabsorbable staple line reinforcement ) . intraoperative methylene blue test was routinely performed at the end of the procedure to check for gastric leak and to evaluate the volume and the shape of the sleeve and a drain was routinely placed . the resected stomach was extracted in a retrieval bag . the cgm sensor ( medtronic ipro 2 digital recorder , mmt-7741 ) was attached to the abdomen of the patients by a serter and was held in place for 6 days . the first cgms calibration was performed 1  h after initialization using blood from a finger prick . by using a glucometer , patients were asked to record three daily glycemic measurements in a diary that were necessary to obtain correct calibration of the recorder . the cgm profiles of the patients were then analyzed with software that enables automatic extraction of the necessary data and subsequent generation of graphs and the area under the curves . on day 6 , the subjects returned to the hospital in the morning in fasting state for an oral glucose tolerance test ( ogtt ) ; measurement of plasma glucose at 0-30-60-90-120 was performed during the cgm ; and the cgm was stopped 2 hours after glucose load . in each patient the total auc for glycemia during ogtt was calculated . during the cgm , the percentage of time conventionally spent in physiological range ( 70140  mg / dl ) , under the physiological range ( < 70  mg / dl ) , and in the hyperglycemic range ( > 140  mg / dl ) was assessed . auc ( area under the curve ) above the limit of 140  mg / dl and auc below the limit of 70  mg / dl were calculated during the cgm . in addition , standard deviation , as index for glycemic variability , glycemic peaks , and nadir during daily life , was evaluated . the study was reviewed and approved by the institutional human ethics committee in accordance with national guidelines and the provisions of the helsinki declaration , as revised in 2000 . all patients provided written informed consent to participate in the study , and additional written informed consent was obtained before any surgical procedure . clinical characteristics of the study participants were reported as mean and sd for continuous variables and frequencies and percentages for categorical variables . chicago , il , usa ) . statistical significance was set at p < 0.05 . all patients included in the study had been defined as cured according to the international criteria for diabetes remission . anthropometric and biochemical parameters and diabetes duration and treatment , before and after lsg , are reported in table 1 . the data obtained by cgm were analyzed and showed a very different pattern of glycemic curves , suggesting that we differentiate patients with hyperglycemic values ( conventionally defined > 140  mg / dl ) from the others who did not spend time in hyperglycemia . therefore , we divided subjects into two groups.group a : patients who spent no time with glycemia over 140  mg / dl ( example of cgm of one patient of this group is reported in figure 1(a)).group b : patients who spent part of their time in hyperglycemia , defined over 140  mg / dl ( example of cgm of one patient of this group is reported in figure 1(b)).patients of group a were defined as  cured  of diabetes and patients of group b were defined as  not cured . group a : patients who spent no time with glycemia over 140  mg / dl ( example of cgm of one patient of this group is reported in figure 1(a ) ) . group b : patients who spent part of their time in hyperglycemia , defined over 140  mg / dl ( example of cgm of one patient of this group is reported in figure 1(b ) ) . glycemic peak and nadir during cgm are reported for both groups of patients in table 2 . in patients of group a ( 8/20 ) , 2  h ogtt showed physiologic glycemic peak at 30 minutes and at 120 glycemia was < 140  mg / dl . these patients were then considered  cured  of diabetes either by international criteria for diabetes remission for bariatric patients or by ogtt criteria , showing a normal glucose tolerance . in these subjects , during everyday life conditions , glycemia assessed by cgm never exceeded the 140  mg / dl levels . in patients of group b ( 12/20 ) , 2  h ogtt showed a delayed glycemic peak not earlier than 60 minutes and sometimes delayed at 90 minutes ; 8 out of 12 patients of this group achieved normal levels at 120 ogtt ( < 140  mg / dl ) , whilst the other patients remained higher than 200  mg / dl as usually occurs in diabetic patients . these patients spent from 13% to 45% of time with glycemia higher than 140  mg / dl during the cgm . therefore , even if these patients showed a normal fasting glucose and normal a1c values , we decided to define them as  not cured  from diabetes . 2  h ogtt glycemic levels in each single patient of both groups are reported in figure 2 . international criteria to exclude diabetes ( fasting glycemia , a1c ) and data obtained from ogtt and cgm in groups a and b are reported in table 2 . the 2  h ogtt glycemia auc in the two intervals of 0120 minutes and 090 minutes has been calculated and added in table 2 in groups a and b. the interval of 090 minutes has been investigated in consideration of the rapid gastric emptying due to lsg . retrospective assessment of anthropometric parameters , insulin use , a1c , fasting plasma c - peptide as marker of insulin secreting ability before surgery , and duration of diabetes was then compared in groups a and b as reported in table 3 . since the pioneering reports of the last decade of the twentieth century [ 22 , 23 ] , the efficacy of bariatric procedures in improving and even normalizing glucose levels in obese patients with type 2 diabetes has been confirmed by a large number of observational studies . however , while fasting plasma glucose concentrations are usually normalized in these patients , little is known about their glucose profiles throughout the day and particularly after meals . in literature , there are only a few reports that adopt cgm following bariatric surgery , mainly aiming to assess hypoglycemia due to dumping syndrome after gastric bypass [ 17 , 18 ] . this study adds something new to the knowledge of glucose variability and tolerance using the cgm and ogtt in patients that underwent lsg . it aims to assess glycemia throughout the day , as a means of investigating the real remission of diabetes , considering that fasting glucose and a1c might be insufficient to exclude the persistence or relapse of diabetes after surgery . according to international guidelines on the definition of glycemic outcomes after bariatric surgery , all patients of this study had been defined as  cured  from diabetes 3 years after lsg . however , we found that an unexpected 60% of these patients experienced significant hyperglycemia revealed by cgm during their everyday life , and in some cases overt diabetes was seen with glycemia > 200  mg / dl at 120 minutes of ogtt . the results obtained by ogtt and cgm allowed confirming that patients appear really cured of diabetes only in group a ( 40% ) . in fact according to cgm these patients spent no time with glycemia over 140  mg / dl , even after meals . surprisingly , a number of patients ( group b ) showed variable time with glycemia over 140 during cgm , often associated with very high glycemic postprandial levels , lasting approximately 40% of daily time . they also had a delayed glycemic peak at 60 minutes after oral glucose load which remained high until 90 minutes . in literature , data are not available to clarify the correct interpretation of ogtt after bariatric surgery ; the lack of this information might be one of the reasons the test is not included in the criteria of diabetes remission in bariatric operated patients . in our opinion , it is not reasonable to apply the standard ogtt criteria in operated subjects because the surgical procedure causes modified glucose kinetics due to an accelerated transit of food in the stomach . in  cured patients , who did not spend any time in hyperglycemia during cgm , glycemic ogtt peak occurred at the first measurement at 30 minutes , while at 90 minutes these patients showed glycemic values similar to basal values . on the contrary , in  not cured patients , who spent a long time in hyperglycemia during cgm , the glycemic peak during ogtt occurred at 6090 minutes with very high values . this effect demonstrates impaired insulin secretion in these patients as suggested by preoperative c - peptide levels . the massive secretory response of beta - cells to these very high and durable glycemic levels is able to rapidly reduce the glycemic levels to values of less than 140  mg / dl , suggesting normal glucose tolerance . therefore , at 2  h after glucose load , plasma glucose determinations may be misleading , and assessment of glycemia at thirty - minute intervals throughout the test is important . four diabetic patients of group b were defined as  cured  according to fasting glycemia and a1c before performing ogtt and cgm , but , in fact , elevated ogtt glycemic values diagnostic for overt diabetes ( glycemia > 200  mg / dl at 120 minutes ) were found . furthermore , these patients spent about 40% of time during cgm with glycemia higher than 140  mg / dl and occasionally even higher than 200  mg / dl . recent studies using cgm showed significant fluctuations in blood glucose values even in patients with excellent a1c plasma levels . these data suggest that glucose variability may have a predictive role for the development of the complications of diabetes [ 25 , 26 ] . moreover kilpatrick et al .   analyzed the diabetes control and complications trial ( dcct ) patient cohort and observed that blood glucose instability is not a predictor of microvascular complications ( mainly retinopathy ) , but , on the other hand , mean daily glucose values , as well as the pre- and postprandial glucose ones , are predictors of cardiovascular disease . found that all - cause and cardiovascular mortality in elderly people with diabetes   were primarily associated with the variability / instability of glucose levels , rather than its absolute values . the clinical use of cgm in this study allowed us to monitor the daily glycemic profile after lsg , which revealed unexpected hyperglycemia . by using cgm we found that only 40% of patients had complete hyperglycemia remission after lsg , although all patients had been considered  cured  according to existing standard definitions of glycemic outcomes after bariatric surgery . our hypothesis is that a1c was not reliable in these cases , probably because of the short duration of hyperglycemic peaks that may have been too rapid for glycation of hemoglobin , even when glycemic peaks were very high . furthermore , we did not observe a balance between hyper- and hypoglycemia , as reported in gastric bypass surgery [ 17 , 18 ] that could explain normal a1c values . in fact , in patients that underwent lsg , the percentage of time spent with glycemia less than 70  mg / dl was only 3.9% in all patients , exactly 5% in group a and 2.6% in group b. in order to identify prognostic factors for complete diabetes remission , we compared the two groups prior to surgery by considering age , diabetes duration , beta - cell function , and insulin use . there is generally agreement among the published studies that patients who have long - standing t2 dm have a lower remission rate after bariatric surgery , probably due to their poor residual beta - cell function . other preoperative patient factors have been associated with the outcomes of diabetes remission , including age , fasting c - peptide concentration , bmi , glycemic control ( a1c ) , and medications used to manage blood glucose , including oral hypoglycemic agents and insulin . as described in a previous study , diabetes duration is the main prognostic factor for diabetes remission after lsg . in fact , we published the fact that patients with history of less than 10 years of diabetes were cured from diabetes , according to standard criteria for diabetes remission ( e.g. , fasting glucose ( < 100  mg / dl ) and a1c ( < 6% ) ) . we observed that although all patients had a duration of diabetes of less than 10 years , patients of group a had a shorter diabetes duration ( maximum 2 years ) than patients of group b. furthermore , patients with diabetes remission after lsg were younger , with higher fasting plasma levels of c - peptide , with higher bmi , and without insulin therapy before surgery . the limits of this study were small sample size and small subgroups according to cgm results , and data was collected only after surgery . further evaluations in a larger number of diabetics with morbid obesity , studied before and after the bariatric surgical operations , will be performed in order to give us more details on this topic . bariatric surgery significantly improves the prognosis of obese patients and improves the overall glycemic control in obese diabetics . we reported glucose variability in a real - life setting for the first time , assessed by cgm after lsg in patients defined as  cured  of diabetes according to international guidelines on remission of diabetes after bariatric procedures . the clinical relevance of this study consists in an insight into glycemia levels in carefully monitored diabetic patients that underwent lsg . we recommend 2  h ogtt , checking glycemia not only at 120 minutes , but also at every 30 minutes , in patients that are apparently cured of diabetes by standard criteria but that are still exposed to significant glucose variability which could cause future chronic complications of diabetic disease .
the study was carried out on type 2 diabetic obese patients who underwent laparoscopic sleeve gastrectomy ( lsg ) . 
 patients underwent regular glycemic controls throughout 3 years and all patients were defined cured from diabetes according to conventional criteria defined as normalization of fasting glucose levels and glycated hemoglobin in absence of antidiabetic therapy . 
 after 3 years of follow - up , continuous glucose monitoring ( cgm ) was performed in each patient to better clarify the remission of diabetes . in this study , we found that the diabetes resolution after lsg occurred in 40% of patients ; in the other 60% , even if they showed a normal fasting glycemia and a1c , patients spent a lot of time in hyperglycemia . during the oral glucose tolerance test ( ogtt ) 
 , we found that 2  h postload glucose determinations revealed overt diabetes only in a small group of patients and might be insufficient to exclude the diagnosis of diabetes in the other patients who spent a lot of time in hyperglycemia , even if they showed a normal glycemia ( < 140  mg / dl ) at 120 minutes ogtt . 
 these interesting data could help clinicians to better individualize patients in which diabetes is not resolved and who could need more attention in order to prevent chronic complications of diabetes .