Β-cell Function Index Research Articles

Adjusting glucose-stimulated insulin secretion for adipose insulin resistance: an index of β-cell function in obese adults.

The hyperbolic relationship between insulin secretion and sensitivity has been used to assess in vivo β-cell function (i.e., the disposition index). The disposition index emphasizes the importance of taking into account both skeletal muscle and hepatic insulin resistance to depict insulin secretion. However, we propose that adipose tissue insulin resistance also needs to be accounted for when characterizing glucose-stimulated insulin secretion (GSIS) because elevated plasma free fatty acids (FFAs) impair β-cell function. To characterize the adipose disposition index, we used [1-(14)C] palmitate infusion to determine basal FFA turnover rate/adipose insulin resistance and an oral glucose tolerance test to characterize the first (i.e., 0-30 min) and second phase (i.e., 60-120 min) of GSIS. We validated a simplified version of the tracer infusion calculation as the product of (1/plasma FFA concentration × plasma insulin concentration) × GSIS in 44 obese insulin-resistant subjects. The plasma FFA and palmitate tracer infusion calculations of the first- and second-phase disposition index were strongly correlated (r = 0.86, P < 0.000001 and r = 0.89, P < 0.000001, respectively). The first- and second-phase adipose disposition index derived from plasma FFA also was tightly associated with fasting hyperglycemia (r = -0.87, P < 0.00001 and r = -0.89, P < 0.00001, respectively) and 2-h glucose concentrations (r = -0.86, P < 0.00001 and r = -0.90, P < 0.00001). Adjusting GSIS for adipose insulin resistance provides an index of β-cell function in obese subjects across the glucose spectrum. Plasma FFA-derived calculations of β-cell function may provide additional insight into the role of adipose tissue in glucose regulation.

AB0334 Methotrexate Reduces Hba1c in Non-Diabetic Patients with Newly Diagnosed Rheumatoid Arthritis or Psoriatic Arthritis

BackgroundRheumatoid arthritis (RA) and psoriatic arthritis (PsA) are associated with an increased risk of diabetes mellitus (DM).1 In patients with RA or PsA disease-modifying anti-rheumatic drugs, including methotrexate (MTX), may...

Effect of canagliflozin, a sodium glucose co-transporter 2 inhibitor, on C-peptide kinetics.

Canagliflozin, a sodium glucose co-transporter 2 inhibitor, improves indices of β-cell function estimated based on circulating C-peptide and glucose concentrations (e.g., Homeostasis Model Assessment [HOMA2-%B], meal tolerance test-based indices). However, use of these β-cell function indices assumes C-peptide kinetics are not altered by canagliflozin. This 2-period crossover study assessed the effect of a single canagliflozin 300-mg dose on C-peptide kinetics in 10 healthy participants. Two hours after receiving canagliflozin or placebo, participants received intravenous somatostatin infusion to suppress endogenous C-peptide secretion and 1 hour later received a bolus injection of synthetic human C-peptide 150 µg. Serum C-peptide was measured over 3 hours and urinary glucose and C-peptide excretion were measured. C-peptide kinetic parameters, including total clearance (CLtotal ) and renal clearance (CLrenal ), were calculated. Serum C-peptide profiles were similar following canagliflozin or placebo treatment. C-peptide CLtotal was slightly lower with canagliflozin versus placebo (mean (SD) of 190 (37) vs. 197 (30) mL/min; canagliflozin/placebo ratio [90% CI] = 96.1% [93.0%; 99.3%]). Other kinetic parameters, including CLrenal , were generally similar between treatments. Results indicate canagliflozin 300 mg does not meaningfully alter C-peptide clearance or other kinetic parameters; therefore, C-peptide-based measurements of insulin secretion are appropriate for assessing β-cell function in canagliflozin-treated participants.

Vigorous physical activity may be important for the insulin sensitivity in immigrants from the Middle East and native Swedes.

To compare physical activity measures and their associations with insulin sensitivity, β-cell function and body mass index (BMI) between Iraqi immigrants and native Swedes. A cross-sectional study of 493 Iraqis (58% men) and 469 Swedes (54% men) aged 30 to 75 years living in the city of Malmö, Sweden. Accelerometry was used for physical activity measures (sedentary time, breaks in sedentary time, moderate and vigorous physical activity, total counts). Insulin sensitivity index and oral disposal index were determined from an oral glucose tolerance test and BMI by body weight and height. Iraqi men were less physically active than Swedish men, while the physical activity was more similar in the women. BMI was a strong predictor of insulin sensitivity and β-cell function and frequently associated with the physical activity measures. BMI modified the associations of insulin sensitivity and β-cell function with the physical activity measures to such extent that only VPA and total counts show direct associations with insulin sensitivity in addition to the indirect associations via BMI. Iraqi women demonstrated weaker associations compared with Swedish women. Physical activity and performed at vigorous intensity may be important mainly for the insulin sensitivity in Iraqi immigrants and native Swedes.

Correlations between A1c, fasting glucose, 2h postload glucose, and β-cell function in the Chinese population

This study was aimed to assess the associations of hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), and 2h postload plasma glucose (2hPG) with β-cell function in the Chinese population. A total of 913 subjects underwent 75-g oral glucose tolerance test (OGTT) and HbA1c testing. According to OGTT, isolated impaired fasting glucose (i-IFG) was defined as 5.6mmol/l≤FPG<7.0mmol/l and 2hPG<7.8mmol/l; isolated impaired glucose tolerance (i-IGT) was defined as FPG<5.6mmol/l and 7.8mmol/l≤2hPG<11.1mmol/l. HbA1c 5.7-6.4% was used to identify subjects with prediabetes. Insulin release was calculated by basal homeostasis model assessment of insulin secretion (HOMA-β), early-phase InsAUC30/GluAUC30, and total-phase InsAUC120/GluAUC120. β-cell function relative to insulin sensitivity was expressed as disposition index (DI). All indices of insulin sensitivity and β-cell function gradually decreased with increasing HbA1c, FPG, and 2hPG (all p<0.01). β-cell function decreased precipitously when HbA1c exceeded 5.5%. Compared with HbA1c, FPG showed stronger correlations with HOMA-β, InsAUC30/GluAUC30, InsAUC120/GluAUC120, DI30, and DI120 (all p<0.05), and 2hPG was more closely related to DI30 and DI120 (all p<0.01). Moreover, FPG was more strongly related to HOMA-β and InsAUC30/GluAUC30 than 2hPG (all p<0.05). The combination of i-IFG and HbA1c 5.7-6.4% showed the greatest reduction in DI30 and DI120 compared with HbA1c 5.7-6.4% alone, i-IGT, or i-IFG (p<0.05). In conclusion, HbA1c could be used as a marker to identify subjects with impaired β-cell function, but OGTT performs better than HbA1c. The combination of HbA1c and FPG is a simple and sensitive method to evaluate β-cell function.

The effect of glargine versus glimepiride on pancreatic β-cell function in patients with type 2 diabetes uncontrolled on metformin monotherapy: open-label, randomized, controlled study

The aim of present study is to assess whether if basal insulin, glargine, could improve insulin secretory function of β-cells compared with glimepiride when metformin alone was failed. This was an open-label and multi-center study for 52 weeks in Korean patients with uncontrolled type 2 diabetes by metformin monotherapy. Subjects were randomized to glargine or glimepiride groups (n = 38 vs. 36, respectively). The primary endpoint was to compare changes in c-peptide via glucagon test after 48 weeks. Glycemic efficacy and safety endpoints (glycated hemoglobin (HbA1c), HOMA-B, fasting plasma glucose (FPG), lipid profiles, and hypoglycemic events) were also checked. The mean disease duration of all subjects was 88.2 months. Changes in C-peptide was no significant different between groups (P = 0.73), even though insulin secretion was not worsened in both groups at the endpoint. Glargine was not superior to glimepiride in other β-cell function indexes such as HOMA-B (P = 0.28). HbA1c and FPG reduced significantly in each groups but not different between two groups. Although, severe hypoglycemia did not occur, symptomatic hypoglycemia was more frequent in glimepiride group (P = 0.01). Insulin glargine was as effective as glimepiride in controlling hyperglycemia and maintaining β-cell function in Korean patients with type 2 diabetes during 48 weeks study period, after failure of metformin monotherapy. Hypoglycemic profile was favorable in the insulin glargine group and less weight gain was observed in the glimepiride group. Our results suggest that glargine and glimepiride can be considered after failure of metformin monotherapy.

Biochemical efficacy of vitamin D in ameliorating endocrine and metabolic disorders in diabetic rats

Context: Due to the biochemical role of vitamin D (Vit D) in the endocrine system, especially its potential anti-inflammatory and immune-modulating properties, there is an increased interest in its potential role in the prevention and control of diabetes mellitus.Objective: This study evaluated the potential therapeutic efficacy of Vit D in averting the detrimental effects of both types of diabetes mellitus.Materials and methods: A total of 50 male Wistar rats were allotted into five groups: a placebo group; a nongenetic model of type 1 diabetes in rats (T1D), injected with a single dose of streptozotocin (STZ; 65 mg/kg, ip); a nongenetic model of type 2 diabetes in rats (T2D), given a short-term high-fat diet followed by a single low dose of STZ (35 mg/kg, ip); fourth and fifth groups that were gastrogavaged with Vit D (10 IU/kg) three days after the induction of T1D and T2D, respectively, which was continued daily throughout the experiment.Results: Vit D (10 IU/kg/60 days) significantly (p < 0.05) decreased fasting plasma glucose, ketoacidosis (decreased non-esterified fatty acid and β-hydroxyl butyric acid), pro-inflammatory interleukin-6, HbA1c in T1D and T2D and insulin resistance index by 33% in T2D. Interestingly, Vit D significantly (p < 0.05) increased fasting plasma insulin by 144% in T1D, plasma Ca level, insulin sensitivity index, and β-cell function index in T1D and T2D.Discussion and conclusion: Vit D ameliorated the deleterious biochemical impact of diabetes mellitus, likely by increasing insulin secretion and sensitivity, ameliorating the β-cell function, and decreasing the number of pro-inflammatory cytokines and insulin resistance.

Case-control study on the risk factors of type 2 diabetes of Dong nationality in Western Hunan

To explore the risk factors of type 2 diabetes mellitus (T2DM) of Dong nationality in Western Hunan, and to provide a scientific basis for the prevention and treatment of T2DM in the district. In the case-control study, the subjects were divided into a T2DM group, an impaired glucose regulation (IGR) group and a normal glucose tolerance (NGT) group through oral glucose tolerance test (OGTT). A questionnaire survey was conducted, and physical measurements and the detection of blood glucose, blood lipids and serum insulin were done. Univariate analysis found significant difference in age, fasting insulin (FINS), HOMA insulin resistance index (HOMA-IRI), HOMA β-cell function index (HOMA-βC), trigalloyl glycerol (TG), high density lipoprotein cholesterol (HDL-C), systolic blood pressure, and diastolic blood pressure in the glucose metabolism among different groups (P<0.05). Body mass index (BMI), waist/hip ratio (WHR), family history of diabetes, number of physical activities per week, dinner taste, fat and protein-rich foods, fresh vegetables and fruits intake were associated with T2DM. Multifactor non-conditional ordinal logistic regression indicated that age was the risk factor of T2DM and IGR. Compared with the group whose age was≤50, the odds ratios of the groups of 50<age≤60, 60<age≤70 and age>>70 were 1.85, 2.83 and 2.64 respectively, P<0.05. The risk of suffering from diabetes of the overweighted or obese people was 2.13 times that of a normal BMI group, P<0.01. The other influencing factors included WHR (OR=2.06), family history of diabetes (OR=11.36), and fat and protein-rich foods (OR=1.90). The main influencing factors of T2DM of Dong nationality in Western Hunan include age, BMI, WHR, family history of diabetes, fat and protein-rich foods. We must strengthen the health eduation of T2DM of Dong nationality in Western Hunan to reduce the risk of T2DM.

Resistance training improves indices of muscle insulin sensitivity and β-cell function in overweight/obese, sedentary young men.

We examined the effects of RT on oral glucose tolerance test (OGTT)-derived indices of muscle insulin sensitivity, hepatic insulin resistance, β-cell function, and skeletal muscle proteins related to glucose transport in overweight/obese, sedentary young men. Twenty-eight participants [median body mass index (BMI) 30.9 kg/m(2); age 22 yr] completed 12 wk of RT (3 sessions/wk) and were assessed for changes in OGTT-derived indices, resting metabolic rate, body composition, serum adipokines, and skeletal muscle protein content [hexokinase 2 (HK2), glucose transporter type 4 (GLUT4), RAC-β serine/threonine-protein kinase (AKT2), glycogen synthase kinase 3β, and insulin receptor substrate 1]. Individualized responses to RT were also evaluated. RT significantly improved insulin and glucose area under the curve (both P < 0.03). With the use of OGTT indices of insulin action, we noted improved muscle insulin sensitivity index (mISI; P = 0.03) and oral disposition index (P = 0.03). BMI, lean body mass (LBM), and relative strength also increased (all P < 0.03), as did skeletal muscle protein content of HK2, GLUT4, and AKT2 (26-33%; all P < 0.02). Hepatic insulin resistance index, adiponectin, leptin, and total amylin did not change. Further analysis demonstrated the presence of highly individualized responsiveness to RT for glucose tolerance and other outcomes. RT improved oral indices of muscle insulin sensitivity and β-cell function but not hepatic insulin resistance in overweight/obese young men. In addition to the increase in LBM, the improvements in insulin action may be due, in part, to increases in key insulin signaling proteins.

Sucralose Affects Glycemic and Hormonal Responses to an Oral Glucose Load

OBJECTIVENonnutritive sweeteners (NNS), such as sucralose, have been reported to have metabolic effects in animal models. However, the relevance of these findings to human subjects is not clear. We evaluated the acute effects of sucralose ingestion on the metabolic response to an oral glucose load in obese subjects.RESEARCH DESIGN AND METHODSSeventeen obese subjects (BMI 42.3 ± 1.6 kg/m2) who did not use NNS and were insulin sensitive (based on a homeostasis model assessment of insulin resistance score ≤2.6) underwent a 5-h modified oral glucose tolerance test on two separate occasions preceded by consuming either sucralose (experimental condition) or water (control condition) 10 min before the glucose load in a randomized crossover design. Indices of β-cell function, insulin sensitivity (SI), and insulin clearance rates were estimated by using minimal models of glucose, insulin, and C-peptide kinetics.RESULTSCompared with the control condition, sucralose ingestion caused 1) a greater incremental increase in peak plasma glucose concentrations (4.2 ± 0.2 vs. 4.8 ± 0.3 mmol/L; P = 0.03), 2) a 20 ± 8% greater incremental increase in insulin area under the curve (AUC) (P < 0.03), 3) a 22 ± 7% greater peak insulin secretion rate (P < 0.02), 4) a 7 ± 4% decrease in insulin clearance (P = 0.04), and 5) a 23 ± 20% decrease in SI (P = 0.01). There were no significant differences between conditions in active glucagon-like peptide 1, glucose-dependent insulinotropic polypeptide, glucagon incremental AUC, or indices of the sensitivity of the β-cell response to glucose.CONCLUSIONSThese data demonstrate that sucralose affects the glycemic and insulin responses to an oral glucose load in obese people who do not normally consume NNS.

Evaluation of oral glucose tolerance test, β-cell function and adverse obstetric outcomes

This study was conducted in order to investigate the prevalence of impaired glucose tolerance (IGT) and gestational diabetes mellitus (GDM), their effect on pregnancy and their association with adverse obstetric outcomes. A cross-sectional study was performed on 345 pregnant women, who were screened between the 24th and 28th gestational week with a 75-g oral glucose tolerance test following abnormal results at 1 h after a 50-g oral glucose challenge test. The obstetric outcomes were recorded along with plasma glucose and insulin levels, homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of β-cell function index (HOMA-βCFI) and 50 subjects were excluded due to incomplete data recovery. Of the 295 pregnant women, 18.6% (55/295) were diagnosed with GDM and 32% (95/295) with IGT. The GDM group exhibited significantly higher fasting and 1-h blood glucose concentrations compared to the normal glucose tolerance (NGT) and IGT groups (P<0.01). The 2- and 3-h insulin values of the NGT group were significantly lower compared to those of the GDM group (P<0.05, P<0.01). In the IGT group, the 2-h insulin values were higher compared to the NGT group and the 3-h values were significantly higher (P<0.01), similar to the GDM group. There was a tendency for progressively decreased β-cell function and increased HOMA-IR from the NGT to the IGT to the GDM group. The adverse outcomes of pregnancy-induced hypertension, fetal distress, neonatal hyperbilirubinemia, preterm delivery, macrosomia and cesarean delivery indicated an association with HOMA-βCFI and HOMA-IR. In conclusion, these findings suggest a clinical significance of β-cell dysfunction in women with gestational IGT.

Postprandial serum C-peptide to plasma glucose concentration ratio correlates with oral glucose tolerance test- and glucose clamp-based disposition indexes

ObjectiveThe C-peptide index (CPI), a ratio of serum C-peptide to plasma glucose levels, is a readily measured index of β-cell function. The difference in the physiological features reflected by the index measured under fasting (F-CPI) or postprandial (PP-CPI) conditions has remained unclear, however. Materials/MethodsWe investigated the relationship of the two CPIs to indexes of insulin secretion measured with an oral glucose tolerance test (OGTT) or with hyperglycemic and hyperinsulinemic–euglycemic clamp analyses as well as to disposition indexes (indexes of insulin secretion adjusted for insulin sensitivity) calculated from OGTT- or clamp-based analyses. We also examined the relationship between glucose tolerance and the clamp-based disposition index. ResultsThe clamp-based disposition index declined progressively from normal glucose tolerance to impaired glucose tolerance to Type 2 diabetes, and it strongly correlated with the 2-h plasma glucose level during an OGTT. For patients with Type 2 diabetes, both F-CPI and PP-CPI correlated with indexes of insulin secretion including HOMA-β, the insulinogenic index, the ratio of the area under the insulin curve to that under the glucose curve during an OGTT, the serum C-peptide level after glucagon challenge, as well as early and total insulin secretion measured with a hyperglycemic clamp. PP-CPI, but not F-CPI, was significantly correlated with clamp-based and OGTT-based disposition indexes. ConclusionsF-CPI was correlated only with unadjusted indexes of insulin secretion, whereas PP-CPI was correlated with such indexes as well as with those adjusted for insulin sensitivity. The better clinical utility of PP-CPI might be attributable to these physiological characteristics.

Variation in Inflammatory Markers and Glycemic Parameters After 12 Months of Exenatide Plus Metformin Treatment Compared with Metformin Alone: A Randomized Placebo-Controlled Trial

To evaluate the effects of exenatide on some inflammatory markers and to quantify the effect of exenatide on β-cell function. A randomized, double-blind, placebo-controlled trial. Seven hospitals in Italy. A total of 174 white treatment-naive adults with type 2 diabetes and a glycated hemoglobin (HbA(1c)) level higher than 7.5%. After an open-label run-in period of 8 ± 2 months with metformin, patients were randomized to take exenatide (5 μg twice/day for the first 4 weeks, 10 μg twice/day thereafter) or a placebo volume equivalent for 12 months. Body mass index, HbA(1c), fasting plasma glucose, postprandial plasma glucose, fasting plasma insulin (FPI), homeostasis model assessment insulin resistance index, homeostasis model assessment β-cell function index (HOMA-β), fasting plasma proinsulin (FPPr), proinsulin-to-fasting plasma insulin ratio (Pr:FPI ratio), C-peptide, glucagon, vaspin, chemerin, and resistin were evaluated at baseline, at randomization, and at 3, 6, 9, and 12 months. Patients also underwent a combined euglycemic, hyperinsulinemic, and hyperglycemic clamp with subsequent arginine stimulation to assess insulin sensitivity and insulin secretion. HbA(1c) was significantly improved with exenatide plus metformin compared with placebo plus metformin. Exenatide plus metformin was also significantly more effective than placebo plus metformin in increasing HOMA-β C-peptide, and all measures of β-cell function after the euglycemic hyperinsulinemic and hyperglycemic clamp. We observed that exenatide plus metformin also reduced resistin compared with placebo plus metformin. No variations in vaspin and chemerin were noted in group-to-group comparisons. We observed a significant correlation between M value increase, an index of insulin sensitivity, and a decrease in inflammatory parameters in the exenatide plus metformin group. The combination of exenatide plus metformin was more effective than metformin alone in improving glycemic control, β-cell function, and inflammatory parameters.

Mercury Exposure in Young Adulthood and Incidence of Diabetes Later in Life

OBJECTIVELaboratory studies suggest that exposure to methylmercury at a level similar to those found in fish may induce pancreatic islet β-cell dysfunction. Few, if any, human studies have examined the association between mercury exposure and diabetes incidence. We examined whether toenail mercury levels are associated with incidence of diabetes in a large prospective cohort.RESEACH DESIGN AND METHODSA prospective cohort of 3,875 American young adults, aged 20–32 years, free of diabetes in 1987 (baseline), were enrolled and followed six times until 2005. Baseline toenail mercury levels were measured with instrumental neutron-activation analysis. Incident diabetes was identified by plasma glucose levels, oral glucose tolerance tests, hemoglobin A1C levels, and/or antidiabetes medications.RESULTSA total of 288 incident cases of diabetes occurred over 18 years of follow-up. In multivariate analyses adjusted for age, sex, ethnicity, study center, education, smoking status, alcohol consumption, physical activity, family history of diabetes, intakes of long-chain n-3 fatty acids and magnesium, and toenail selenium, toenail mercury levels were positively associated with the incidence of diabetes. The hazard ratio (95% CI) of incident diabetes compared the highest to the lowest quintiles of mercury exposure was 1.65 (1.07–2.56; P for trend = 0.02). Higher mercury exposure at baseline was also significantly associated with decreased homeostasis model assessment of β-cell function index (P for trend < 0.01).CONCLUSIONSOur results are consistent with findings from laboratory studies and provide longitudinal human data suggesting that people with high mercury exposure in young adulthood may have elevated risk of diabetes later in life.

Glucose Intolerance Is Associated With Increased Intimal-Medial Thickness of the Carotid Artery and Increased Pulse-Wave Velocity in Renal Transplant Recipients

BackgroundAlthough new-onset diabetes after transplantation has been demonstrated to have a significant negative impact on allograft and patient survival, the role of glucose intolerance (impaired fasting glucose [IFG] and/or impaired glucose tolerance [IGT], as asymptomatic hyperglycemia and borderline diabetes, has not been identified in renal transplant recipients. MethodsWe enrolled 32 renal transplant recipients (at least 1year after transplantation) without prior evidence of diabetes at our institution in this study. Transplant recipients were divided into 2 groups (normal glucose tolerance group and glucose intolerance group) according to the results of their oral glucose tolerance test with 75 g of glucose. Glucose intolerance included IFG, IGT, and IFG/IGT. Normal glucose tolerance was detected in 19 patients, and glucose intolerance in 13: had 6 IGT, 2 IFG, and 5 IGT/IFG. Bilateral brachial-ankle pulse-wave velocity (baPWV) and intimal-media thickness (IMT) measured as markers of atherosclerosis were compared between the 2 groups. Insulin resistance was estimated with the homeostasis model assessment of insulin resistance (HOMA-R), and pancreatic β-cell function evaluated by the homeostasis model assessment of β-cell function and insulinogenic index. ResultsThe patients in the glucose intolerance group showed significantly greater baPWV and IMT than those in the normal glucose tolerance group. HOMA-R in the glucose intolerance patients was significantly higher than in the normal glucose tolerance patients. Linear regression analysis showed the increased IMT in the renal transplant recipients to be significantly correlated with HOMA-R. ConclusionsRenal transplant recipients with glucose intolerance had increased IMT and baPWV, suggesting that glucose intolerance in renal transplant recipients may induce atherosclerosis and that the rise in insulin resistance may contribute to the increased IMT in renal transplant recipients.

25-Hydroxyvitamin D is closely related with the function of the pancreatic islet β cells

This study is to investigate the relationship between 25-Hydroxyvitamin D (25-OH-D) and pancreatic islet β cell function under different glucose tolerance statuses in China. Totally, 180 patients with type 2 diabetes mellitus (DM group), 178 patients with impaired fasting glucose/impaired glucose tolerance (IFG/IGT group), and 160 normal control subjects (NGT group) were included to measure their body parameters and biochemical parameters. In oral glucose tolerance test, fasting serum 25-OH-D was assessed by the enzyme-linked immunosorbent assay (ELISA). Homeostasis model assessment for insulin resistance (Homa-IR), insulin acuity index (IAI), β-cell function index (Homa-BCF) as well as secretion index (IS) were determined. The levels of 25-OH-D, IAI and Homa-BCF in the DM group and IFG/IGT group were significantly lower than that in NGT group (P < 0.05). Homa-IR in DM group and IFG/IGT group was significantly higher than that in the NGT group (P < 0.05). Pearson correlation analysis and partial correlation analysis showed that 25-OH-D was positively correlated with fasting insulin (FINS) and Homa-BCF (P < 0.05). Multiple stepwise regression analysis showed that 25-OH-D was one of the influential factors of pancreatic islet β cell function in patients with type 2 diabetes mellitus. Our results suggest that 25-OH-D is closely related with the function of the pancreatic islet β cells and is one of the influential factors of pancreatic islet β cell function.

Defining criteria for the introduction of liraglutide using the glucagon stimulation test in patients with type2 diabetes.

To define a set of criteria using indices of β-cell function, including results from the glucagon stimulation test, for liraglutide introduction in patients with type2 diabetes. In the present retrospective cohort study, patients were included in our analysis if their β-cell function had been evaluated with a glucagon stimulation test and a 24-h urinary C-peptide (U-CPR) excretion test before switching from insulin therapy to liraglutide monotherapy. The efficacy of liraglutide was determined by the extent to which glycemic control was achieved or if glycated hemoglobin levels were maintained at <7.0% after liraglutide monotherapy for 24weeks. Liraglutide was effective in 36 of 77 patients. In the liraglutide-effective cases, the following parameters were higher: fasting C-peptide (CPR0) levels, C-peptide levels 6min after glucagon stimulation (CPR6), the C-peptide index (CPI; CPR0×100/fasting plasma glucose) and stimulated C-peptide index (S-CPI; CPR6×100/plasma glucose 6min after glucagon stimulation). U-CPR did not differ between liraglutide-effective and liraglutide-ineffective cases. Using receiver operating characteristic analysis adjusted for baseline characteristics, the independent cut-off value for effective liraglutide introduction was 0.72 for CPI and 1.92 for S-CPI. Evaluation of β-cell function using the glucagon stimulation test is useful for determining the efficacy of liraglutide introduction in patients with type2 diabetes.

Relative contributions of insulin resistance and β‐cell dysfunction to the development of Type 2 diabetes in Koreans

Controversies still exist regarding the relative contributions of insulin resistance and β-cell dysfunction to the pathogenesis of Type 2 diabetes in different populations. We examined the associations of baseline insulin resistance and β-cell function indices with the development of Type 2 diabetes in Koreans. We analysed the clinical and laboratory data of 17 878 Korean adults (age 20-79 years) who underwent routine medical examinations with a median interval of 3.5 years (range 2.5-4.7 years). Using the homeostasis model assessment, insulin resistance (HOMA-IR) and β-cell function (HOMA-%B) indices at baseline were assessed. Those who developed diabetes (n = 732, 4.1%) had significantly higher fasting serum insulin level (53.4 ± 31.2 vs. 41.4 ± 23.4 pmol/l) and HOMA-IR (2.38 ± 1.45 vs. 1.65 ± 1.02) and lower HOMA-%B (74 ± 47 vs. 85 ± 48) at baseline (P < 0.001 for all). Both high HOMA-IR and low HOMA-%B were independently associated with an increased odds ratio of incident Type 2 diabetes. Among the participants who developed diabetes, 29% demonstrated predominant β-cell dysfunction (HOMA-%B < 25th percentile) and 51% had predominant insulin resistance (HOMA-IR > 75th percentile). When we divided the participants according to the median BMI of the whole population (23.7 kg/m²), 49% of participants in the low BMI group demonstrated predominant β-cell dysfunction and 26% had predominant insulin resistance, whilst 21% in the high BMI group demonstrated mainly β-cell dysfunction and 60% had mainly insulin resistance. In individuals with low BMI, β-cell dysfunction is the predominant defect, whereas insulin resistance is the predominant pathogenetic factor in individuals with high BMI in the development of Type 2 diabetes in Koreans.

Canagliflozin, a Sodium Glucose co-transporter 2 (SGLT2) inhibitor, improves indices of β-cell function in patients with type 2 diabetes on metformin plus sulphonylurea

Question: Progressive loss of β-cell function (βCF) is thought to underlie the pathophysiology of type 2 diabetes mellitus (T2DM). Canagliflozin (CANA), an inhibitor of SGLT2, is in development for the treatment of T2DM. In hyperglycaemic, partially pancreatectomised rats, βCF can be restored when normoglycaemia is achieved with SGLT2 inhibitor treatment. In a Phase 3 study, 26 weeks of CANA monotherapy treatment improved glycaemic control and indices of βCF in patients with T2DM inadequately controlled with diet and exercise. To further assess the effects of CANA on βCF, indices of βCF were evaluated in a Phase 3 study of patients with T2DM inadequately controlled with metformin (MET) + sulphonylurea (SU).

Early Metabolic Markers of the Development of Dysglycemia and Type 2 Diabetes and Their Physiological Significance

Metabolomic screening of fasting plasma from nondiabetic subjects identified α-hydroxybutyrate (α-HB) and linoleoyl-glycerophosphocholine (L-GPC) as joint markers of insulin resistance (IR) and glucose intolerance. To test the predictivity of α-HB and L-GPC for incident dysglycemia, α-HB and L-GPC measurements were obtained in two observational cohorts, comprising 1,261 nondiabetic participants from the Relationship between Insulin Sensitivity and Cardiovascular Disease (RISC) study and 2,580 from the Botnia Prospective Study, with 3-year and 9.5-year follow-up data, respectively. In both cohorts, α-HB was a positive correlate and L-GPC a negative correlate of insulin sensitivity, with α-HB reciprocally related to indices of β-cell function derived from the oral glucose tolerance test (OGTT). In follow-up, α-HB was a positive predictor (adjusted odds ratios 1.25 [95% CI 1.00–1.60] and 1.26 [1.07–1.48], respectively, for each standard deviation of predictor), and L-GPC was a negative predictor (0.64 [0.48–0.85] and 0.67 [0.54–0.84]) of dysglycemia (RISC) or type 2 diabetes (Botnia), independent of familial diabetes, sex, age, BMI, and fasting glucose. Corresponding areas under the receiver operating characteristic curve were 0.791 (RISC) and 0.783 (Botnia), similar in accuracy when substituting α-HB and L-GPC with 2-h OGTT glucose concentrations. When their activity was examined, α-HB inhibited and L-GPC stimulated glucose-induced insulin release in INS-1e cells. α-HB and L-GPC are independent predictors of worsening glucose tolerance, physiologically consistent with a joint signature of IR and β-cell dysfunction.