Higher Glucose Excursions Research Articles

Imprecision nutrition? Different simultaneous continuous glucose monitors provide discordant meal rankings for incremental postprandial glucose in subjects without diabetes

High postprandial glucose excursions may increase risk for disease. Individuals have widely varying glucose responses to different meals, and precision nutrition approaches often seek to personalize diets to minimize postprandial glycemic responses as measured by continuous glucose monitors (CGMs). However, it is unknown whether different CGM devices result in concordant meal rankings according to postprandial glycemic excursions. We explored whether meal rankings according to postprandial glycemic excursions differ between 2 simultaneously worn CGMs. We collected 27,489 simultaneous measurements from Dexcom G4 Platinum and Abbott Freestyle Libre Pro CGMs during 28 inpatient days in 16 adults without diabetes. Simultaneous glucose measurements obtained for 2 h following 760 ad libitum meals were used to compare within-subject meal rankings between the CGM devices according to their incremental glucose response. Postprandial responses to ad libitum meals were highly variable, with the Abbott and Dexcom systems resulting in within-subject incremental mean ± SD glucose CVs of 91.7±1.9% and 94.2±2.7%, respectively. Within-subject meal rankings for incremental glycemic responses were relatively discordant between CGMs, with a mean Kendall rank correlation coefficient of 0.43±0.05. Meals in the bottom compared with those in the top half of incremental glycemic responses ranked by Abbott resulted in 50±10% (P=0.0002) less glycemic reduction as measured by Dexcom, and vice versa. The missing glycemic reduction by eating meals ranked according to the discordant CGM was inversely correlated with each subject's Kendall rank correlation coefficient (r = -0.95; P<0.0001). Precision nutrition approaches that use CGMs to personalize meal recommendations for minimizing glycemic excursions may be premature given the discordance of within-subject meal rankings between simultaneous CGM devices. More research is needed to clarify the source of this imprecision. This trial was registered at clinicaltrials.gov as NCT03407053.

1870-P: Glucose Metabolism after Overnight and Prolonged Fasting in Participants with Different Glucose Tolerances

Background: Metabolic regulation of glucose can be altered by fasting periods. The aim of our study was to examine the glucose metabolism after an overnight fast (12 hours) as well as after prolonged fasting (36 hours of fasting) in non-obese people, people with obesity and people with type 2 diabetes (T2DM). Material and Methods: Glucose metabolism was assessed by a 75 g oral glucose tolerance test after 12 and 36 hours fasting, respectively. Area under the curve (AUC) was calculated according to the trapezoidal rule. Insulin sensitivity was estimated by using QUICKI and HOMA-IR. Results: In total 60 participants (age 43±16 years, 62% women) were included. Fasting levels of glucose, insulin and c-peptide were significantly lower in all cohorts after 36 hours vs. 12 hours of fasting (p&amp;lt;0.05). However, in non-obese people mean 2h-glucose level was significant higher after prolonged fasting [108.7±31.1 mg/dL vs. 79.4±18.4mg/dL after 12h fasting; p&amp;lt;0.05] with significantly lower 30 minutes insulin levels following prolonged fasting, while within the two other cohorts no change in this 2h-glucose was observed. Indices of insulin sensitivity improved in all groups after prolonged fasting. Conclusion: Our data demonstrate higher glucose excursions and a reduced early insulin response after 36 hours of fasting compared to an overnight fasting period in participants with various glucose tolerance levels. Disclosure N.J. Tripolt: None. P.N. Pferschy: None. A. Obermayer: None. M.L. Eckstein: Research Support; Self; Dexcom, Inc., Novo Nordisk A/S, Sanofi-Aventis. H. Kojzar: None. C. Sourij: None. O. Moser: Other Relationship; Self; Dexcom, Inc., Novo Nordisk A/S, Sanofi. B.M. Obermayer-Pietsch: None. R. Riedl: None. H. Sourij: Advisory Panel; Self; Amgen, AstraZeneca, Boehringer Ingelheim International GmbH, Merck Sharp &amp; Dohme Corp., Novo Nordisk A/S, Sanofi. Research Support; Self; Boehringer Ingelheim International GmbH, Merck Sharp &amp; Dohme Corp., Novo Nordisk A/S, Sanofi. Speaker’s Bureau; Self; Boehringer Ingelheim International GmbH, Novo Nordisk A/S, Sanofi.

Does Human Milk Insulin Help Program Infant Pancreatic Function? Variation in Neonatal Human Milk Insulin Is Associated with Later Measures of Infant Glycemic Control

Abstract Objectives Whether variation in human milk (HM) insulin contributes to neonatal blood sugar regulation and pancreatic programming remains unknown. This pilot study investigates whether HM insulin concentrations correlate with infant pancreatic function in exclusively breastfed 5-month old infants. We hypothesize that neonatal exposure to elevated HM insulin will “under stimulate” the infant pancreas, resulting in an exaggerated glycemic response to oral glucose at 5 months. Methods Exclusively breastfed infants of normoglycemic mothers (NG; n = 5) and mothers with minor insulin resistance (IR; n = 5) were administered a 1.75 g/kg oral glucose challenge. Infant capillary glucose was assessed at Fasting (&amp;gt;2 hours), 30 minutes (T30) and 60 minute (T60) after glucose administration. Fasting HM insulin was measured at 2-weeks and 5-months. Repeated Measures ANOVA and linear regression analyses were utilized. Results Using repeated measures analysis, the IR group exhibited a more dramatic glycemic response to the glucose challenge (P = 0.031): exhibiting lower fasting glucose (P = 0.085; n = 10) and higher glucose excursion from fasting to T30 (P = 0.007) compared to the NG group. HM insulin did not differ between the NW and IR groups at 2-weeks or 5-months. However, higher HM insulin concentrations at 2-weeks did correlate with a more dramatic infant glycemic response to oral glucose at 5 months. Fasting HM insulin at 2 weeks was positively associated with infant glucose at T30 (P = 0.033) and with the increase in glucose from fasting to T30 (P = 0.081; n = 8). Furthermore, fasting HM insulin at 2-weeks was negatively associated with infant glucose at T60 (P = 0.031) and the change in glucose from T30-T60 (P = 0.032; n = 7). Conclusions These pilot results suggest that HM insulin may contribute to postnatal programming of infant pancreatic function such that chronic exposure to elevated HM insulin may result in a dampened pancreatic response to an oral glucose challenge. Confirmation in a larger sample size is necessary. Funding Sources NIH/NIDDK; The Gerber Foundation.

Indian reality of managing type 2 diabetes: an expert review of global and national guidelines for optimum insulin use

Several guidelines provide recommendations on insulin therapy in people with type 2 diabetes mellitus (T2DM). Major global guidelines have been adapted in multiple countries, and local consensus recommendations have been published giving guidance on insulin therapy considering local realities. This expert review focuses on the recommendations from global and Indian guidelines on insulin therapy in people with T2DM. It emphasizes on a patient-centric approach, including the glycemic parameters, psychosocial aspects, phase of life, and the Indian realities of T2DM management in guiding optimum insulin therapy for initiation and intensification. Therapeutic inertia towards timely insulin initiation needs to be bridged. Owing to the high carbohydrate diet and high postprandial glucose (PPG) excursions, insulin co-formulation and premix insulins offering total glycemic control can be preferred for a timely insulin initiation in Indians with T2DM that is uncontrolled despite multiple oral antidiabetic drugs. They also provide simplicity and convenience for insulin initiation and intensification. Among basal insulins, insulin degludec and glargine U300 are found to be safer, and offer more dosing flexibility than the first-generation basal insulin analogs. Faster-acting insulin aspart has been shown to provide better PPG control and dosing flexibility compared to a rapid-acting insulin analog with a lower risk of hypoglycemia. Thus, based on available evidences, a preferred use of insulin analog over conventional human insulins is suggested, keeping cost considerations in mind. The review also discusses optimum use of concomitant medications with insulin therapy for T2DM management.

74-LB: Impact of Mild and Moderate High Blood Glucose Excursions on Daily Living in Adults with Type 1 Diabetes

Introduction: Severe hyperglycemic events and diabetic ketoacidosis (DKA) have significant effects on daily activity however, the effect of mild and moderate glucose excursions on functioning and quality of life (QoL) remains unknown. This study aimed to assess the impact of these excursions on well-being in a well-managed population with type 1 diabetes (T1D) using survey and CGM data. Methods: Adults with T1D (N = 71), 68.6% female, 93.2% white, aged 44.11 years, average A1c 6.51%, with diabetes for 26.65 years, completed an online survey through T1D Exchange Glu and uploaded CGM data via Tidepool. Results: Moderate high blood glucose (HBG) excursions were most strongly related to QoL (WHO-5) and happiness (Subjective Happiness Scale, SHS). Participants with fewer mild (&amp;gt; 180 mg/dL) HBG excursions had higher WHO-5 scores indicating better QoL when controlling for income and duration of diabetes. Participants who had longer durations in the same range, regardless if it was time in range or mild or moderate hyperglycemia, had higher SHS scores indicating greater happiness when controlled for income and duration of diabetes. Conclusions: This study illustrates the impact of mild HBG excursions and glycemic variability on QoL in people with T1D. HBG excursions were related to QoL and glycemic variability was related to happiness further supporting the urgency to decrease the amount of time hyperglycemic. These results indicate the need to increase time in range and decrease overall blood glucose variability. A limitation includes convenience sampling in a very well-managed population. Future research should further investigate the relationships of these factors in a diverse sample. Disclosure A. Hughes: None. J. Bispham: None. C. Garey: None. J. Liu: None. L. Fuller: None. E.T. Nykaza: None. J.A. Meno: None. A. McAuliffe-Fogarty: None.

Glycemic Variability: Risk Factors, Assessment, and Control.

Glycemic variability (GV) a well-established risk factor for hypoglycemia and a suspected risk factor for diabetes complications. GV is also a marker of the instability of a person's metabolic system, expressed as frequent high and low glucose excursions and overall volatile glycemic control. In this review, the author discusses topics related to the assessment, quantification, and optimal control of diabetes, including (1) the notion that optimal control of diabetes, that is, lowering of HbA1c-the commonly accepted gold-standard outcome-can be achieved only if accompanied by simultaneous reduction of GV; (2) assessment and visualization of the two principal dimensions of GV, amplitude and time, which is now possible via continuous glucose monitoring (CGM) and various metrics quantifying GV and the risks associated with hypo- and hyperglycemic excursions; and (3) the evolution of diabetes science and technology beyond quantifying GV and into the realm of GV control via pharmacological agents, for example, GLP-1 receptor agonists and DPP-4 inhibitors, which have pronounced variability-reducing effect, or real-time automated closed-loop systems commonly referred to as the "artificial pancreas." The author concludes that CGM allows close tracking over time, and therefore precise quantification, of glycemic variability in diabetes. The next step-optimal control of glucose fluctuations-is also taken by medications with pronounced GV-lowering effect primarily in type 2 diabetes, and by automated insulin delivery in type 1 diabetes. Contemporary CGM-based artificial pancreas systems use specific GV representations as input signals, and thus their main objective is to minimize GV and, from there, optimize glycemic control.

Unmethylated Insulin DNA Is Elevated After Total Pancreatectomy With Islet Autotransplantation: Assessment of a Novel Beta Cell Marker.

Beta cell death may occur both after islet isolation and during infusion back into recipients undergoing total pancreatectomy with islet autotransplantation (TPIAT) for chronic pancreatitis. We measured the novel beta cell death marker unmethylated insulin (INS) DNA in TPIAT recipients before and immediately after islet infusion (n = 21) and again 90 days after TPIAT, concurrent with metabolic functional assessments (n = 25). As expected, INS DNA decreased after pancreatectomy (p = 0.0002). All TPIAT recipients had an elevated unmethylated INS DNA ratio in the first hours following islet infusion. In four samples (three patients), INS DNA was also assessed immediately after islet isolation and again before islet infusion to assess the impact of the isolation process: Unmethylated and methylated INS DNA fractions both increased over this interval, suggesting death of beta cells and exocrine tissue before islet infusion. Higher glucose excursion with mixed-meal tolerance testing was associated with persistently elevated INS DNA at day 90. In conclusion, we observed universal early elevations in the beta cell death marker INS DNA after TPIAT, with pronounced elevations in the islet supernatant before infusion, likely reflecting beta cell death induced by islet isolation. Persistent posttransplant elevation of INS DNA predicted greater hyperglycemia at 90 days.

Both Dietary Protein and Fat Increase Postprandial Glucose Excursions in Children With Type 1 Diabetes, and the Effect Is Additive

OBJECTIVETo determine the separate and combined effects of high-protein (HP) and high-fat (HF) meals, with the same carbohydrate content, on postprandial glycemia in children using intensive insulin therapy (IIT).RESEARCH DESIGN AND METHODSThirty-three subjects aged 8–17 years were given 4 test breakfasts with the same carbohydrate amount but varying protein and fat quantities: low fat (LF)/low protein (LP), LF/HP, HF/LP, and HF/HP. LF and HF meals contained 4 g and 35 g fat. LP and HP meals contained 5 g and 40 g protein. An individually standardized insulin dose was given for each meal. Postprandial glycemia was assessed by 5-h continuous glucose monitoring.RESULTSCompared with the LF/LP meal, mean glucose excursions were greater from 180 min after the LF/HP meal (2.4 mmol/L [95% CI 1.1–3.7] vs. 0.5 mmol/L [−0.8 to 1.8]; P = 0.02) and from 210 min after the HF/LP meal (1.8 mmol/L [0.3–3.2] vs. −0.5 mmol/L [−1.9 to 0.8]; P = 0.01). The HF/HP meal resulted in higher glucose excursions from 180 min to 300 min (P < 0.04) compared with all other meals. There was a reduction in the risk of hypoglycemia after the HP meals (odds ratio 0.16 [95% CI 0.06–0.41]; P < 0.001).CONCLUSIONSMeals high in protein or fat increase glucose excursions in youth using IIT from 3 h to 5 h postmeal. Protein and fat have an additive impact on the delayed postprandial glycemic rise. Protein had a protective effect on the development of hypoglycemia.

Pleiotropic and Age-dependent Effects of Decreased Protein Modification by O-Linked N-Acetylglucosamine on Pancreatic β-Cell Function and Vascularization

The hexosamine biosynthesis pathway (HBP) regulates the post-translational modification of nuclear and cytoplasmic protein by O-linked N-acetylglucosamine (O-GlcNAc). Numerous studies have demonstrated increased flux through this pathway contributes to the development of β-cell dysfunction. The effect of decreased O-GlcNAc on the maintenance of normal β-cell function, however, is not well understood. We studied transgenic mice that over express β-N-acetylglucosaminidase (O-GlcNAcase), an enzyme that catalyzes the removal of O-GlcNAc from proteins, in the pancreatic β-cell under control of the rat insulin promoter. 3-4-Month-old O-GlcNAcase transgenic mice have higher glucose excursions with a concomitant decrease in circulating insulin levels, insulin mRNA levels, and total islet insulin content. In older (8-9-month-old) O-GlcNAcase transgenic mice glucose tolerance is no longer impaired. This is associated with increased serum insulin, islet insulin content, and insulin mRNA in the O-GlcNAcase transgenic mice. These improvements in β-cell function with aging are associated with increased angiogenesis and increased VEGF expression, with parallel increases in activation of Akt and expression of PGC1α. The biphasic effects as a function of age are consistent with published observations of mice with increased O-GlcNAc in islets and demonstrate that O-GlcNAc signaling exerts multiple effects on both insulin secretion and islet survival.

First-Phase Insulin Secretion Has Limited Impact on Postprandial Glycemia in Subjects with Type 2 Diabetes: Correlations Between Hyperglycemic Glucose Clamp and Meal Test

Lack of first-phase insulin (INS) secretion is regarded as causative for high postprandial glucose excursions in subjects with type 2 diabetes. We aimed to determine the impact of early INS secretion on postprandial glycemia. Twenty subjects with type 2 diabetes (age 54 +/- 8 years, body mass index 28.7 +/- 2.7 kg/m(2) [mean +/- SD]) underwent a hyperglycemic glucose clamp and a meal test twice separated by a washout period of 4 weeks. Multiple regression analysis was used to identify determinants of postprandial glycemia. During hyperglycemic glucose clamps eight subjects showed a preserved first-phase INS secretion (P1+), whereas 12 subjects showed none (P1-). Both subject groups differed in fasting blood glucose (BG) (116 +/- 7 vs. 147 +/- 31 mg/dL, P = 0.011) and glycosylated hemoglobin (6.0 +/- 0.4 vs. 6.7 +/- 0.8, P = 0.041). Total INS secretory response during glucose clamps was higher in P1+ than P1- (INS-area under the concentration vs. time curve [AUC](0-120 min) 6.7 +/- 2.7 vs. 3.2 +/- 2.1 mU.min/mL; P = 0.006). During meal tests, however, INS-AUC(0-120 min) was similar between P1+ and P1-, whereas early INS secretion was still different (INS-AUC(0-60 min) 3.9 +/- 1.8 vs. 2.1 +/- 1.0 mU.min/mL; P = 0.031). Despite higher INS-AUC(0-60 min) in P1+, early postprandial BG was comparable between groups (BG-AUC(0-60 min) 1.5 +/- 0.5 vs. 1.6 +/- 0.6 g.min/dL; difference not significant). Multiple regression analyses showed no impact of first-phase INS secretion on postprandial glycemia, either in P1+ or in P1-. Nevertheless, in P1-, but not in P1+, postprandial glycemia was negatively correlated with INS sensitivity (R(2) = 0.83, P < 0.001). This study, correlating results of hyperglycemic glucose clamps with meal tests, shows that a preserved first-phase INS secretion has only a limited impact on postprandial glucose excursions in a group of subjects in early-stage type 2 diabetes.

Excess glycaemic excursions after an oral glucose tolerance test compared with a mixed meal challenge and self‐measured home glucose profiles: is the OGTT a valid predictor of postprandial hyperglycaemia and vice versa?

Postprandial hyperglycaemia is often assumed in individuals with high glucose excursions during an oral glucose tolerance test (OGTT), but the relationship between glucose levels during the OGTT and after a mixed meal is yet unclear. We addressed whether (i) glucose concentrations after an oral glucose load are similar to those after a test meal or under daily life conditions and (ii) impaired glucose tolerance (IGT) predicts postprandial hyperglycaemia. A total of 60 subjects with normal (NGT), IGT or diabetic (DM) glucose tolerance were examined with an OGTT, a mixed meal challenge (3433 kJ) and a self-determined 10-point home glucose profile. There was a significant correlation between the 120-min OGTT glucose levels and the glycaemic excursions after the test meal and during everyday conditions. However, glucose excursions during the OGTT exceeded those after the test meal and during everyday conditions by approximately 20 and approximately 30% respectively. Likewise, insulin and C-peptide levels rose to higher levels after oral glucose compared with mixed meal ingestion. The mean self-determined diurnal glucose levels were already 10% higher in subjects with IGT compared with NGT subjects (p < 0.0001). Glucose levels reached after an oral glucose challenge and during real life are correlated to some extent, but the absolute levels of glycaemia greatly differ between both conditions. Therefore, 'postchallenge' glucose levels measured during an OGTT might be used as a predictor of 'postprandial hyperglycaemia', but caution should be taken when both terms are used synonymously. Furthermore, subjects with IGT during an OGTT already exhibit increased postprandial glucose levels under real-life conditions. This suggests that IGT should already be considered an overt disease condition rather than merely a high-risk situation.

Continuous Glucose Monitoring in Cystic Fibrosis Patients According to the Glucose Tolerance

Cystic fibrosis (CF) is associated with a long preclinical state of abnormal glucose tolerance. The aim of this study was (i) to evaluate the profile of glucose tolerance in young adults with CF and (ii) to compare these results with those obtained by a continuous subcutaneous glucose monitoring (CGMS). CF subjects with fasting glycemia inferior to 126 mg/dl were included in the study. An oral glucose tolerance test (OGTT) identified the subjects either with a normal glucose tolerance (NGT), or impaired glucose tolerance (IGT), or diabetes. CGMS (Medtronic) was performed during 3 days to analyze mean glucose level, high glucose excursions, and glucose area under the curve (AUC). Forty-nine patients were included in the study. NGT (n=22), IGT (n=17), and diabetes groups (n=10) were comparable except with regard to age and BMI (p<0.001). HbA1c values in diabetes group were significantly higher (p<0.001) than in NGT and IGT groups. CGMS revealed peaks of glucose values superior to 200 mg/dl at least once after a meal in 8 patients (36%) with NGT, in 9 patients (52%) with IGT, and in all patients with diabetes (p<0.01). Mean CGMS glucose and glucose AUC values increased in patients with diabetes compared to patients with NGT and IGT (p<0.05). Peak of CGMS glucose reached 182+/-60 mg/dl in NGT group despite the normal glucose profile at OGTT. In conclusion, CGMS revealed pathological glucose excursions not only in patients with impaired glucose tolerance at OGTT but also in patients with a normal glycemic profile. CGMS could be a useful tool for the early detection of hyperglycemia in patients with CF.

Evaluation of a New Measure of Blood Glucose Variability in Diabetes

Recent studies show the importance of controlling blood glucose variability in relationship to both reducing hypoglycemia and attenuating the risk for cardiovascular and behavioral complications due to hyperglycemia. It is therefore important to design variability measures that are equally predictive of low and high blood glucose excursions. We introduce the average daily risk range (ADRR), a variability measure computed from routine self-monitored blood glucose (SMBG) data. The ADRR was constructed using a development dataset for 39 and 31 adults with type 1 and type 2 diabetes, respectively. The formula was then fixed, and the ADRR was compared against other variability measures using an independent validation dataset containing approximately 4 months of SMBG for 254 and 81 adults with type 1 and type 2 diabetes. From the 1st month of validation SMBG data, we computed the ADRR, blood glucose SD and coefficient of variation, daily blood glucose range and interquartile range, mean amplitude of glycemic excursion, M-value, and lability index. Then all measures were tested as predictors of low blood glucose (<2.2 mmol/l; <3.9 mmol/l) and high (>10 mmol/l; >22.2 mmol/l) events in the subsequent 3 months. The ADRR was the best predictor of both hypoglycemia and hyperglycemia, with a 6-fold increase in the likelihood of hypoglycemia and 3.5-fold increase in the likelihood of hyperglycemia across its risk categories. In a large SMBG database, the ADRR showed strong association with subsequent out-of-control glucose readings. Compared with other variability measures, the ADRR demonstrated a superior balance of sensitivity to predicting both hypoglycemia and hyperglycemia. This prediction was independent from type of diabetes.

Morning hyperglycemic excursions: a constant failure in the metabolic control of non-insulin-using patients with type 2 diabetes.

To determine whether, over daytime, one or several hyperglycemic excursions exist that can be general failures in the glycemic control of patients with type 2 diabetes. In 200 non-insulin-using patients with type 2 diabetes, diurnal plasma glucose and insulin profiles were studied. Plasma glucose concentrations were measured after an overnight fast (at 8:00 A.M. immediately before breakfast), during the postprandial period (at 11:00 A.M. and 2:00 P.M.), and during the postabsorptive period (at 5:00 P.M., extended postlunch time). In the population considered as a whole, prelunch glucose concentrations (12.0 mmol/l) were found to be significantly increased (P < 0.0001) when compared with those observed at 8:00 A.M. (8.8 mmol/l), at 2:00 P.M. (10.5 mmol/l), and at 5:00 P.M. (8.6 mmol/l). Similar significant excursions (P < 0.0001) in prelunch glucose were observed within subsets of patients selected from the following criteria: 1) body weight, 2) HbA(1c), 3) categories of treatment, and 4) residual beta-cell function. From the calculation of areas under the daytime glucose curves, the relative contributions of postprandial and fasting glucose to the total glucose increment were found to be similar. High plasma glucose excursions over morning periods seem to be a permanent failure in non-insulin-using patients with type 2 diabetes, whatever the clinical (BMI), biological (HbA(1c)), therapeutic, and pathophysiological (residual beta-cell function) status. Midmorning glucose testing should be recommended for detecting such abnormalities and for correcting them with appropriate therapies.

Dietary considerations for obese diabetic subjects.

Individuals with an upper-body form of obesity show greater associations with higher glucose excursions, exacerbated insulin resistance, increased abnormality of lipoprotein profile, and higher cardiovascular risk. Individuals with obesity and diabetes are at great risk for cardiovascular disease. Weight reduction and improvement in blood glucose control through dietary interventions for the obese person with non-insulin-dependent diabetes mellitus (NIDDM) hold the greatest potential for reducing morbidity and mortality. The relative merits of different weight-reduction programs are unclear, but regimens should be nutritionally complete, easy to follow, and include a program for maintaining the reduced weight level. Improvement in insulin action and the possibility of slowing development of clinical nephropathy or end-stage renal disease in NIDDM through weight loss have been found. Very low calorie diets, when used with medical supervision, may lead to significant weight loss, improved metabolic status, and even reduction or elimination of the need for oral hypoglycemic agents or insulin; however, further studies are needed to examine possible negative outcomes in people with NIDDM before very low calorie diets can be recommended. The causes of obesity and its connection with diabetes are unclear, but even modest calorie restriction may be beneficial to obese diabetic patients because of the positive effects on blood glucose levels and requirements for insulin and oral antidiabetic agents.