Shape Of Glucose Response Curve Research Articles

Shape of the OGTT glucose response curve: relationship with β-cell function and differences by sex, race, and BMI in adults with early type 2 diabetes treated with metformin

IntroductionThe shape of the glucose curve during an oral glucose tolerance test (OGTT) reflects β-cell function in populations without diabetes but has not been as well studied in those with...

2297-PUB: The Shape of Glucose Response Curve during Oral Glucose Tolerance Tests (OGTT) and Long-Term Near-Normoglycemia Remission in African Americans Presenting with Hyperglycemic Crises

Approximately 70% of obese African American (AA) patients with new-onset diabetic ketoacidosis (DKA) and severe hyperglycemia (SH) achieve near-normoglycemia remission (defined as HbA1c <7%, fasting blood glucose [BG]< 130 mg/dl, and off insulin for 1 month) with intensive insulin treatment. The shape of glucose response curve during OGTT has been shown predictive of future glycemic failure and beta(β)-cell function in adolescents with diabetes and adults. Biphasic (Bφ) curves showing better glycemic control and β-cell function compared to monophasic (Mφ) or incessant rise (IR) curves. We hypothesize that in AA patients with new-onset DKA and SH, Bφ shape at remission is associated with lower hyperglycemia relapse compared to Mφ or IR curves. Seventy AA patients underwent a 75g two-hour OGTT after near-normoglycemia remission and at end of study (median follow-up, 392 days). Insulin sensitivity (Si, oral minimal model) and β-cell function (AUCi: incremental area under the curve of insulin), and disposition index (Di= Si x AUCi) were compared among the different OGTT response curves. Hyperglycemia relapse-free survival (fasting BG > 130 mg/dl, 2 random BG > 180 mg/dl or HbA1c > 7%) was calculated with Kaplan-Meier curve. At remission, initial OGTT showed 56% of patients with Mφ, 16% with Bφ, and 29% with IR curve shape. Baseline characteristics did not differ. Even though, more patients in the Bφ group (88%) sustained remission than the Mφ (57%) and IR (53%), hyperglycemia relapse-free survival did not differ by curve shape (log rank, p=0.26). On initial OGTT, Si (p=0.09), AUCi (p=0.12) and Di (p=0.06) did not differ between curve shapes. At last OGTT, Si (p=0.43), AUCi (0.47) and Di (p=0.22) did not differ. In obese AA patients with new-onset DKA and SH, the shape of the glucose response curve during OGTT does not predict long-term glycemic control or β-cell function. Disclosure L. Cotten: None. D. Stefanovski: None. O. Oladejo: None. G.E. Umpierrez: None. P. Vellanki: Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc. Funding National Institutes of Health (K08DK0830361, K23DK113241-01A1, UL1TR002378, 1P30DK111024-01)

Glucose lowering and pancreato-protective effects of Abrus Precatorius (L.) leaf extract in normoglycemic and STZ/Nicotinamide – Induced diabetic rats

Ethnopharmacological relevanceAbrus precatorius (L.) leaves are used as folk medicine by the local communities in the western region of Ghana to treat diabetes mellitus; however, this health claim remains unverified scientifically. ObjectiveThe study investigated glucose lowering and pancreato-protective effects of Abrus precatorius leaf extract (APLE) in normoglycemic and STZ/nicotinamide (NIC)-induced diabetic rats.Method: after preparation of APLE, it was subjected to phytochemical screening, proximate composition and elemental assessments by using standard methods. Oral glucose tolerance test (OGTT) and maltose, lactose and sucrose oral challenge were assessed in normoglycemic rats post-APLE. Morphological characteristics of glucose response curve (time of glucose peak and shape of glucose response curve) were determined. Subsequently, diabetes mellitus was experimentally established in normoglycaemic adult Sprague-Dawley rats (weighing 150–250 g) of both sexes by sequential injection of Streptozotocin (STZ, 60 mg/kg ip)-reconstituted in sodium citrate buffer and NIC (110 mg/kg ip)-reconstituted in normal saline (1:1 v/v) for 16 weeks. Except control rats (normal saline 5 ml/kg ip; baseline fasting blood glucose [FBG] of 6.48 mmol/L), rats having FBG (stable at 11.1 mmol/L or ≥ 250 mg/dL) 3 days post-STZ/NIC injection were randomly re-assigned to one of the following groups: model (STZ/NIC-induced diabetic rats), APLE (100, 200 and 400 mg/kg respectively po) and metformin (300 mg/kg po) and treated daily for 28 days. Bodyweight and FBG were measured on weekly basis. FBG was measured by using standard glucometers. On day 28, rats were sacrificed under chloroform anesthesia, blood collected via cardiac puncture; kidney, liver and pancreas surgically harvested. While the pancreas was processed, sectioned and H&E-stained for histological examination, fresh kidney and liver were homogenized for assessment of total anti-oxidant capacity. Median cross-sectional area of pancreatic islets of Langerhans was determined for each group by using Amscope. ResultsCumulatively, APLE (100, 200 and 400 mg/kg respectively) dose-dependently decreased the initial FBG by 55.22, 76.15 and 77.77% respectively compared to model (−1.04%) and metformin (72.29%) groups. APLE treatment recovered damaged pancreatic β-cells and also increased median cross-sectional area (x106 μm2) of pancreatic islets compared to that of model group. APLE significantly (P < 0.05) increased total anti-oxidant capacity (5.21 ± 0.02 AscAE μg/mL) of plasma, kidney and liver compared to model (4.06 ± 0.04 AscAE μg/mL) and metformin (4.87 ± 0.03 AscAE μg/mL) groups. ConclusionAPLE has demonstrated glucose lowering and pancreato-protective effects in rats and arrested the characteristic loss in bodyweight associated with diabetes mellitus. This finding preliminarily confirms folk use of APLE as an anti-diabetic herbal medicine, whiles providing a rationale for further translational studies on APLE.

The shape of the glucose response curve during an oral glucose tolerance test heralds \u03b2\u2013cell function in a large Chinese population

BackgroundThe shape of the glucose response curve during an oral glucose tolerance test (OGTT) can predict β-cell function and insulin resistance. However, there have been few studies conducted on Chinese people. Thus, we aimed to verify the usefulness of the glucose response curve in a large Chinese population.MethodsA total of 9059 OGTT (3-h tests) were categorized into either a monophasic or a multiphasic group based on the shape of the glucose response. Homeostasis model assessments of fasting insulin resistance, the Matsuda Index, the insulinogenic index, and the disposition index were assessed by plasma glucose and serum insulin concentration obtained at fasting or during an OGTT.ResultsThe shape of the OGTT glucose response curve was monophasic in 87.3% and multiphasic in 12.7% of participants. Individuals in the multiphasic group were younger compared to those in the monophasic group (38.6 ± 13.6 vs. 35.4 ± 13.5, P < 0.001). Individuals in the monophasic group had significantly higher fasting plasma glucose (FPG 5.6 ± 13.5 vs. 5.2 ± 0.6, P < 0.001), fasting insulin (FINS 14.8 ± 8.7 vs. 13.5 ± 7.9, P < 0.01), and homeostasis model assessment of insulin resistance (HOMA-IR 3.8 ± 2.6 vs. 3.1 ± 2.0, P < 0.001) and impaired β-cell function (disposition index 12.7 ± 14.1 vs. 16.6 ± 17.8, P < 0.001) compared to those in the multiphasic group.ConclusionThe monophasic OGTT glucose response curve could reflect impaired β-cell function in a large Chinese population.

The Shape of the Glucose Response Curve During an Oral Glucose Tolerance Test: Forerunner of Heightened Glycemic Failure Rates and Accelerated Decline in β-Cell Function in TODAY.

Obese youth without diabetes with monophasic oral glucose tolerance test (OGTT) glucose response curves have lower insulin sensitivity and impaired β-cell function compared with those with biphasic curves. The OGTT glucose response curve has not been studied in youth-onset type 2 diabetes. Here we test the hypothesis that the OGTT glucose response curve at randomization in youth in the TODAY (Treatment Options for Type 2 Diabetes in Adolescents and Youth) study forecasts heightened glycemic failure rates and accelerated decline in β-cell function. OGTTs (n = 662) performed at randomization were categorized as monophasic, biphasic, or incessant increase. Demographics, insulin sensitivity (1/fasting insulin), C-peptide index (△C30/△G30), and β-cell function relative to insulin sensitivity (oral disposition index [oDI]) were compared among the three groups. At randomization, 21.7% had incessant increase, 68.6% monophasic, and 9.7% biphasic glucose response curves. The incessant increase group had similar insulin sensitivity but significantly lower C-peptide index and lower oDI, despite similar diabetes duration, compared with the other two groups. Glycemic failure rates were higher in the incessant increase group (58.3%) versus the monophasic group (42.3%) versus the biphasic group (39.1%) (P < 0.0001). The 6-month decline in C-peptide index (32.8% vs. 18.1% vs. 13.2%) and oDI (32.2% vs. 11.6% vs. 9.1%) was greatest in incessant increase versus monophasic and biphasic with no difference in insulin sensitivity. In the TODAY study cohort, an incessant increase in the OGTT glucose response curve at randomization reflects reduced β-cell function and foretells increased glycemic failure rates with accelerated deterioration in β-cell function independent of diabetes duration and treatment assignment compared with monophasic and biphasic curves. The shape of the OGTT glucose response curve could be a metabolic biomarker prognosticating the response to therapy in youth with type 2 diabetes.

The Shape of the Glucose Response Curve during an Oral Glucose Tolerance Test Was Associated with Muscle Insulin Sensitivity and Visceral Fat Accumulation in Nonobese Healthy Men

Previous studies reported that the shape of glucose response curve during an oral glucose tolerance test (OGTT) could be a marker of insulin sensitivity in obese subjects. The biphasic response curve was defined by a second rise in glucose concentration of &amp;gt;4.5mg/dl after the decline in glucose during OGTT and subjects with biphasic response curve were insulin sensitive and had low risk of type 2 diabetes compared with subjects with monophasic response curve. While type 2 diabetes is often developed in non-obese Asians, it is still unclear whether the subjects with biphasic response curve are also insulin sensitive in non-obese healthy men. To clarify this, we studied 49 non-obese (BMI&amp;lt;25 kg/m2) healthy Japanese men. We evaluated insulin sensitivity in muscle and liver by 2-step hyperinsulinemic euglycemic clamp. We also measured ectopic fat in muscle and liver and subcutaneous and viscera fat areas by 1H-MRS and MRI, respectively. Based on the shape of glucose response curve during OGTT, we divided the subjects into monophasic (n=31) and biphasic group (n=18). The 60- and 90-min glucose levels were significantly lower in biphasic group than monophasic group (60-min:157.5±30.9 vs. 126.4±31.3mg/dl, p&amp;lt;0.01, 90-min:123.4±23.4 vs. 103.8±20.6mg/dl, p&amp;lt;0.01), while glucose levels at other time points and insulinogenic index were comparable between the groups. In addition, biphasic group showed lower visceral fat area (82.7±27.8 vs. 62.6±24.2 cm2, P=0.014) and higher muscle insulin sensitivity (0.22±0.vs. 0.27±0.09 mg/kg FFM·min-1 ·μU-1·ml, P&amp;lt;0.020) compared with monophasic group. Ectopic fat accumulation in muscle and liver, subcutaneous fat area and hepatic insulin sensitivity were comparable between the groups. In conclusion, biphasic glucose response curve is a marker of elevated muscle insulin sensitivity with less visceral fat in non-obese Japanese healthy men. Disclosure H. Kaga: None. Y. Tamura: None. K. Takeno: None. S. Kakehi: None. Y. Someya: None. R. Suzuki: None. S. Kadowaki: None. D. Sugimoto: None. Y. Furukawa: None. T. Funayama: None. R. Kawamori: None. H. Watada: Advisory Panel; Self; AstraZeneca. Consultant; Self; Astellas Pharma US, Inc., AstraZeneca, Boehringer Ingelheim GmbH, Daiichi Sankyo Company, Limited, Sumitomo Dainippon Pharma Co., Ltd., Eli Lilly and Company, Kissei Pharmaceutical Co., Ltd., Kowa Pharmaceuticals America, Inc., Kyowa Hakko Kirin Co., Ltd., Merck Sharp &amp; Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk A/S, Novartis AG, Ono Pharmaceutical Co., Ltd., Sanofi, Sanwa Kagaku Kenkyusho Co., Ltd., Takeda Development Center Asia, Pte. Ltd.. Research Support; Self; Abbott, Astellas Pharma US, Inc., AstraZeneca, Bayer AG, Benefit One Health Care Co., Ltd., Boehringer Ingelheim GmbH, Bristol-Myers Squibb Company, Daiichi Sankyo Company, Limited, Sumitomo Dainippon Pharma Co., Ltd., Eli Lilly and Company, Kissei Pharmaceutical Co., Ltd., Kowa Pharmaceuticals America, Inc., Kyowa Hakko Kirin Co., Ltd., Johnson &amp; Johnson Diabetes Institute, LLC., Merck Sharp &amp; Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co., Ltd., Nitto Boseki Co., Ltd., Novartis AG, Novo Nordisk A/S, Ono Pharmaceutical Co., Ltd., Pfizer Inc., Sanofi, Sanwa Kagaku Kenkyusho Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Development Center Asia, Pte. Ltd., Terumo Medical Corporation.