Glycemic Variability in Patients With Early Type 2 Diabetes: The Impact of Improvement in β-Cell Function

Kramer, Caroline; Choi, Haysook; Zinman, Bernard; Retnakaran, Ravi

doi:10.2337/dc13-2591

Cited by 59 publications

(57 citation statements)

References 38 publications

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“…Lastly, b-cell function and insulin sensitivity were assessed with surrogate indices, rather than more time-consuming and cumbersome clamp studies, which would have been difficult to implement in 494 new mothers on two occasions in the first year after delivery. Moreover, ISSI-2 and Matsuda index are validated measures that have been widely used in previous studies (10,11,23,(32)(33)(34)(35).…”

Section: Discussionmentioning

confidence: 99%

“…ISSI-2 is a validated measure of b-cell function that is analogous to the disposition index obtained from the intravenous glucose tolerance test (30,31). ISSI-2 has been directly validated against the disposition index from the intravenous glucose tolerance test, with which it exhibits stronger correlation than do other OGTT-derived measures of b-cell function (31), and has been used to measure b-cell function in several previous studies, including both clinical trials and observational studies (10,23,(32)(33)(34)(35). ISSI-2 is defined as the product of 1) insulin secretion measured by the ratio of AUC ins to AUC gluc and 2) insulin sensitivity measured by Matsuda index (30,31).…”

Section: Laboratory Measurements and Physiologic Indicesmentioning

confidence: 99%

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Prospective Associations of Vitamin D Status With β-Cell Function, Insulin Sensitivity, and Glycemia: The Impact of Parathyroid Hormone Status

et al. 2014

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Previous studies have yielded conflicting findings on the relationship between low vitamin D (25-OH-D) and impaired glucose homeostasis. In this context, we hypothesized that combined assessment of 25-OH-D with its regulator parathyroid hormone (PTH) may be required for optimal evaluation of the impact of vitamin D status on glucose metabolism. Thus, we evaluated the prospective associations of 25-OH-D and PTH at 3 months postpartum with b-cell function (Insulin SecretionSensitivity Index-2 [ISSI-2]), insulin sensitivity (Matsuda index), and glycemia at 12 months postpartum in 494 women undergoing serial metabolic characterization. Notably, 32% of those with prediabetes/diabetes mellitus at 12 months postpartum had both vitamin D deficiency and PTH in the highest tertile at 3 months postpartum. On multiple-adjusted linear regression analyses, vitamin D deficiency/insufficiency with PTH in the highest tertile at 3 months independently predicted poorer b-cell function (P = 0.03) and insulin sensitivity (P = 0.01) and increased fasting (P = 0.03) and 2-h glucose (P = 0.002) at 12 months postpartum. In contrast, vitamin D deficiency/insufficiency with lower PTH did not predict these outcomes. In conclusion, only vitamin D deficiency/insufficiency with increased PTH is an independent predictor of b-cell dysfunction, insulin resistance, and glycemia, highlighting the need for consideration of the PTH/25-OH-D axis when studying the impact of vitamin D status on glucose homeostasis.

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Section: Discussionmentioning

confidence: 99%

Section: Laboratory Measurements and Physiologic Indicesmentioning

confidence: 99%

Prospective Associations of Vitamin D Status With β-Cell Function, Insulin Sensitivity, and Glycemia: The Impact of Parathyroid Hormone Status

et al. 2014

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“…It was calculated using the 75‐g OGTT PG and PI concentrations as follows: √ (fasting PG × fasting PI × mean PG × mean PI), where PG was expressed in mg/dL (1/18 mmol/L) and PI in μU/mL (6 pmol/L). ISSI‐2 is an OGTT‐derived measure of β‐cell function that has been validated against the disposition index from the frequently sampled intravenous glucose tolerance 34. It was calculated by taking the product of (1) insulin secretion as measured by the ratio of the total area‐under‐the‐insulin‐curve (AUC ins ) to the total area‐under‐the‐glucose curve (AUC glu ), and (2) insulin sensitivity as measured by the Matsuda ISI OGTT .…”

Section: Methodsmentioning

confidence: 99%

The effect of small doses of fructose and allulose on postprandial glucose metabolism in type 2 diabetes: A double‐blind, randomized, controlled, acute feeding, equivalence trial

Noronha

Braunstein

Glenn

et al. 2018

Diabetes Obesity Metabolism

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AimTo assess and compare the effect of small doses of fructose and allulose on postprandial blood glucose regulation in type 2 diabetes.MethodsA double‐blind, multiple‐crossover, randomized, controlled, acute feeding, equivalence trial in 24 participants with type 2 diabetes was conducted. Each participant was randomly assigned six treatments separated by >1‐week washouts. Treatments consisted of fructose or allulose at 0 g (control), 5 g or 10 g added to a 75‐g glucose solution. A standard 75‐g oral glucose tolerance test protocol was followed with blood samples at −30, 0, 30, 60, 90 and 120 minutes. The primary outcome measure was plasma glucose incremental area under the curve (iAUC).ResultsAllulose significantly reduced plasma glucose iAUC by 8% at 10 g compared with 0 g (717.4 ± 38.3 vs. 777.5 ± 39.9 mmol × min/L, P = 0.015) with a linear dose response gradient between the reduction in plasma glucose iAUC and dose (P = 0.016). Allulose also significantly reduced several related secondary and exploratory outcome measures at 5 g (plasma glucose absolute mean and total AUC) and 10 g (plasma glucose absolute mean, absolute and incremental maximum concentration [Cmax], and total AUC) (P < .0125). There was no effect of fructose at any dose. Although allulose showed statistically significant reductions in plasma glucose iAUC compared with fructose at 5 g, 10 g and pooled doses, these reductions were within the pre‐specified equivalence margins of ±20%.ConclusionAllulose, but not fructose, led to modest reductions in the postprandial blood glucose response to oral glucose in individuals with type 2 diabetes. There is a need for long‐term randomized trials to confirm the sustainability of these improvements.

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“…The insulin protocol and patient characteristics before and during the prerandomization IIT phase have been previously described in detail (8,17). In brief, 63 participants stopped taking all antidiabetic medications and completed an overnight fast before undergoing a 2-h 75-g OGTT the next morning.…”

Section: Prerandomization Iit Phasementioning

confidence: 99%

Liraglutide and the Preservation of Pancreatic β-Cell Function in Early Type 2 Diabetes: The LIBRA Trial

et al. 2014

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OBJECTIVEClinical studies evaluating the effects of medications on b-cell function in type 2 diabetes (T2DM) are compromised by an inability to determine the actual baseline degree of b-cell dysfunction independent of the reversible dysfunction induced by hyperglycemia (glucotoxicity). Short-term intensive insulin therapy (IIT) is a strategy for eliminating glucotoxicity before randomization. This study determined whether liraglutide can preserve b-cell function over 48 weeks in early T2DM following initial elimination of glucotoxicity with IIT. RESEARCH DESIGN AND METHODSIn this double-blind, randomized, placebo-controlled trial, 51 patients with T2DM of 2.6 6 1.9 years' duration and an A1C of 6.8 6 0.8% (51 6 8.7 mmol/mol) completed 4 weeks of IIT before randomization to daily subcutaneous liraglutide or placebo injection, with serial assessment of b-cell function by Insulin SecretionSensitivity Index-2 (ISSI-2) on oral glucose tolerance test performed every 12 weeks. RESULTSThe primary outcome of baseline-adjusted ISSI-2 at 48 weeks was higher in the liraglutide group than in the placebo group (339.8 6 27.8 vs. 229.3 6 28.4, P = 0.008). Baseline-adjusted HbA 1c at 48 weeks was lower in the liraglutide group (6.2 6 0.1% vs. 6.6 6 0.1%, P = 0.055) (44 6 1.1 vs. 49 6 1.1 mmol/mol). At each quarterly assessment, >50% of participants on liraglutide had an HbA 1c £6.0% (42 mmol/mol) and glucose tolerance in the nondiabetic range. Despite this level of glycemic control, no difference was found in the incidence of hypoglycemia between the liraglutide and placebo groups (P = 0.61). Two weeks after stopping treatment, however, the beneficial effect on ISSI-2 of liraglutide versus placebo was entirely lost (191.9 6 24.7 vs. 238.1 6 25.2, P = 0.20). CONCLUSIONSLiraglutide provides robust enhancement of b-cell function that is sustained over 48 weeks in early T2DM but lost upon cessation of therapy.The natural history of type 2 diabetes mellitus (T2DM) is characterized by rising glycemia and the need for increased antidiabetic medication over time (1). This clinical course is driven by the progressive deterioration of pancreatic b-cell function, a pathologic process that precedes the diagnosis of T2DM and continues

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Glycemic Variability in Patients With Early Type 2 Diabetes: The Impact of Improvement in β-Cell Function

Cited by 59 publications

References 38 publications

Prospective Associations of Vitamin D Status With β-Cell Function, Insulin Sensitivity, and Glycemia: The Impact of Parathyroid Hormone Status

Prospective Associations of Vitamin D Status With β-Cell Function, Insulin Sensitivity, and Glycemia: The Impact of Parathyroid Hormone Status

The effect of small doses of fructose and allulose on postprandial glucose metabolism in type 2 diabetes: A double‐blind, randomized, controlled, acute feeding, equivalence trial

Liraglutide and the Preservation of Pancreatic β-Cell Function in Early Type 2 Diabetes: The LIBRA Trial

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