OBJECTIVETo determine the mechanism by which the bile acid sequestrant colesevelam improves glycemic control.RESEARCH DESIGN AND METHODSWe performed a frequently sampled intravenous glucose tolerance test (FSIGT) with minimal model analysis and a meal tolerance test (MTT) in 20 subjects with impaired fasting glucose (11 men, 9 women; mean age 60.7 ± 1.9 years, BMI 29.4 ± 0.9 kg/m2) in a single-blind study after 2 weeks of placebo treatment and 8 weeks of colesevelam 3.75 g daily. From these tests, insulin sensitivity, β-cell function, and glucose tolerance were determined, along with gastrointestinal peptide levels during the MTT.RESULTSFasting plasma glucose and HbA1c decreased with colesevelam (from 5.9 ± 0.1 to 5.7 ± 0.1 mmol/L, P < 0.05, and from 5.86 ± 0.06 to 5.76 ± 0.06%, P = 0.01, respectively), but fasting insulin did not change. Colesevelam had no effect on any FSIGT measures. In contrast, the MTT incremental area under the curve (iAUC) for both glucose (from 249.3 ± 28.5 to 198.8 ± 23.6 mmol/L ⋅ min, P < 0.01) and insulin (from 20,130 [13,542–35,292] to 13,086 [9,804–21,138] pmol/L ⋅ min, P < 0.05) decreased with colesevelam. However, the ratio of iAUC insulin to iAUC glucose was not changed. iAUC for cholecystokinin (CCK) increased (from 43.2 [0–130.1] to 127.1 [47.2–295.2] pmol/L ⋅ min, P < 0.01), while iAUC for fibroblast growth factor 19 decreased (from 11,185 [1,346–17,661] to 2,093 [673–6,707] pg/mL ⋅ min, P < 0.01) with colesevelam. However, iAUC for glucagon, glucose-dependent insulinotropic peptide, and glucagon-like peptide 1 did not change.CONCLUSIONSColesevelam improves oral but not intravenous glucose tolerance without changing insulin sensitivity, β-cell function, or incretins. This effect may be at least partially explained by the colesevelam-induced increase in CCK.

F r o m r e s e a r c h t o P r a c t i c e / G ly c e m i c m a r k e r s : a r e v i e w o F t h e t o o l s w e a l l l o v e , P e r h a P s t o o D e a r ly ? In BriefThis article reviews the advantages and limitations of the current glycemic biomarkers, including A1C, 1,5-anhydroglucitol, and the glycated proteins fructosamine and glycated albumin. It provides patient encounter case studies and related discussion to guide health care professionals on the appropriate use of the various glycemic biomarkers in clinical practice.

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Risk of type 1 diabetes at 3 years is high for initially multiple and single Ab+ IT and multiple Ab+ NT. Genetic predisposition, age, and male sex are significant risk factors for development of Ab+ in twins.

Aims/Hypothesis To examine the association of type 2 diabetes mellitus with arm length as a marker for early life environment and development. Methods This was a cross-sectional analysis of 658 second and third generation Japanese Americans (349 men and 309 women). Different arm length (total, upper and forearm length) and leg length (total and lower leg length) measurements were performed. Type 2 diabetes was defined by use of hypoglycemic medication or a fasting plasma glucose (FPG) ≥7mmol/L or 2 h ≥11.1mmol/L during an OGTT. Persons meeting criteria for impaired glucose tolerance were excluded from these analyses (FPG<7mmol/L and 2 h <11.1 and ≥7.8mmol/L). Multivariable logistic regression was used to estimate associations between diabetes prevalence and limb lengths while adjusting for possible confounders. Results 145 subjects had diabetes. On univariate analysis arm and leg length were not associated with diabetes. After adjustment for age, sex, CT measured intra-abdominal fat area, height, weight, smoking status and family history of diabetes, total arm length and upper arm length were inversely related to diabetes (Odds Ratio (OR) for a 1 standard deviation increase 0.49; 95% CI 0.29, 0.84 and OR 0.56; 95% CI 0.36, 0.87, respectively). Forearm length, height and leg length were not associated with diabetes after adjustment for confounding variables. Conclusions/interpretation Our findings of associations between arm lengths and type 2 diabetes prevalence supports a role for factors that determine bone growth or their correlates in the development of this condition.