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Effect of short-term intensive insulin therapy on ?-cell function in patients with newly diagnosed type 2 diabetes.

ABSTRACT: The effect of intensive insulin therapy on hyperglucagonemia in newly diagnosed type 2 diabetes (T2DM), and its associations with ?-cell function, has not been elucidated. This study assessed the effect of 12 weeks of intensive insulin therapy on hyperglucagonemia in newly diagnosed T2DM and its associations with ?-cell function, with reference to the effects of 12 weeks of oral hypoglycemic agents (OHAs).One hundred eight patients with newly diagnosed T2DM were enrolled from January 2015 to December 2015. The patients were randomly divided to receive, for 12 weeks, either intensive insulin therapy or OHAs. Meal tolerance tests were conducted at baseline before treatment (0 week), at 12 weeks (end of treatment), and 12 months after the initiation of treatment. The levels of glucagon, proinsulin, C-peptide (CP), and blood glucose were measured at timepoints 0, 30, and 120 minutes during the meal tolerance test.Intensive insulin treatment was associated with a decrease in glucagon levels (at 0, 30, and 120?minutes) and proinsulin/CP, and an increase in the insulin-secretion index ?CP30/?G30 and ?CP120/?G120, at 12 weeks and 12 months during the follow-up, compared with the corresponding effects of OHAs. Intensive insulin therapy could reduce but failed to normalize glucagon levels at 12 weeks. There were no correlations between the change of percentages in total area under the curve of glucagon and other glycemic parameters (proinsulin/CP; ?CP30/?G30; or ?CP120/?G120). Patients who received intensive insulin therapy were more likely to achieve their target glycemic goal and remission, compared with those who received OHAs.Short-term intensive insulin therapy facilitates the improvement of both ?-cell and ?-cell function in newly diagnosed T2DM mellitus. Decline of ?-cell secretion and concomitant ?-cell dysfunction may both be involved in the pathogenesis of T2DM.

SUBMITTER: Zheng HL

PROVIDER: S-EPMC7440309 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Effect of short-term intensive insulin therapy on α-cell function in patients with newly diagnosed type 2 diabetes.

Zheng Hai-Lan HL Xing Yan Y Li Fan F Ding Wei W Ye Shan-Dong SD

Medicine 20200401 14

The effect of intensive insulin therapy on hyperglucagonemia in newly diagnosed type 2 diabetes (T2DM), and its associations with β-cell function, has not been elucidated. This study assessed the effect of 12 weeks of intensive insulin therapy on hyperglucagonemia in newly diagnosed T2DM and its associations with β-cell function, with reference to the effects of 12 weeks of oral hypoglycemic agents (OHAs).One hundred eight patients with newly diagnosed T2DM were enrolled from January 2015 to Dec ...[more]

PMID: 32243407

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Project description:OBJECTIVE:To assess the efficacy and safety of short- term intensive hypoglycemic therapy with a triple regimen consisting of metformin, sagliptin and dapagliflozin in patients with newly diagnosed type 2 diabetes mellitus with hemoglobin Alc (HbA1c) of 9%-12%. METHODS:We prospectively enrolled 58 patients with newly diagnosed type 2 diabetes, who were treated with metformin combined with sagliptin and dapagliflozin for 12 weeks on the basis of diabetic diet and regular exercise. Blood glucose was monitored during the treatment and the changes in HbA1c, fasting blood glucose (FBG), 2-hour postprandial blood glucose (2 hPBG), fasting insulin (FINS), 2-hour postprandial insulin (2 hPINS), fasting C-peptide (F-CP), 2-hour postprandial C-peptide (2 hP-CP), and body weight after treatment as well as the incidence of hypoglycemia and adverse events associated with the treatment were recorded. RESULTS:Two patients withdrew from the study for intolerance of gastrointestinal reactions, and another 2 withdrew for inconvenience of access to the medicines. Fifty-four of the patients finally completed the study, including 34 male and 20 female patients. After 12 weeks of therapy, all the patients showed significant improvements in FBG, 2 hPBG, HbA1c, HOMA-beta and HOMA-IR (P < 0.001) with a mean reduction of HbA1c level by (4.19 ± 1.07)%, and the goal of HbA1c control to below 7.0% was achieved in 83.33% of the patients. The reduction of HbA1c was correlated with FBG (r=0.487, P=0.000), 2 hPBG (r=0.310, P=0.023), and HOMA-? (r=-0.398, P=0.003). The patients had a mean body weight loss by 2.47±3.38 kg (P < 0.001) and a mean decrease of body mass index (BMI) by 0.90± 1.18 kg/m2 (P < 0.001) after the therapy. The body weight-reducing effect was associated with the patients' baseline body weight (r=0.678, P=0.000), BMI (r=0.818, P=0.000), F-CP (r=0.282, P=0.039) and HOMA-IR (r=0.297, P=0.029). During the therapy 8 patients experienced hypoglycemic symptoms (10 times, 14.81%); 3 patients were diagnosed with hypoglycemia (blood glucose ?3.9 mmol/L, 3 times), and the overall incidence of hypoglycemia was 5.56%. No serious hypoglycemia or infections of the urinary and reproductive systems occurred in these patients. CONCLUSIONS:Short-term intensive oral hypoglycemic therapy with metformin combined with sagliptin and dapagliflozin is effective for treatment of patients with newly diagnosed type 2 diabetes with HbA1c of 9%-12% and shows a good weight-reducing effect with a low risk of hypoglycemia. The combined therapy can effectively improve ?-cell insulin secretion function, and is suitable for treatment of newly diagnosed type 2 diabetic patients with high blood glucose.

Project description:BackgroundThe study was conducted to investigate the effects of metformin treatment on the human gut microbiome's taxonomic and functional profile in the Latvian population, and to evaluate the correlation of these changes with therapeutic efficacy and tolerance.MethodsIn this longitudinal observational study, stool samples for shotgun metagenomic sequencing-based analysis were collected in two cohorts. The first cohort included 35 healthy nondiabetic individuals (metformin dose 2x850mg/day) at three time-points during metformin administration. The second cohort was composed of 50 newly-diagnosed type 2 diabetes patients (metformin dose-determined by an endocrinologist) at two concordant times. Patients were defined as Responders if their HbA1c levels during three months of metformin therapy had decreased by ≥12.6 mmol/mol (1%), while in Non-responders HbA1c were decreased by <12.6 mmol/mol (1%).ResultsMetformin reduced the alpha diversity of microbiota in healthy controls (p = 0.02) but not in T2D patients. At the species level, reduction in the abundance of Clostridium bartlettii and Barnesiella intestinihominis, as well as an increase in the abundance of Parabacteroides distasonis and Oscillibacter unclassified overlapped between both study groups. A large number of group-specific changes in taxonomic and functional profiles was observed. We identified an increased abundance of Prevotella copri (FDR = 0.01) in the Non-Responders subgroup, and enrichment of Enterococcus faecium, Lactococcus lactis, Odoribacter, and Dialister at baseline in the Responders group. Various taxonomic units were associated with the observed incidence of side effects in both cohorts.ConclusionsMetformin effects are different in T2D patients and healthy individuals. Therapy induced changes in the composition of gut microbiome revealed possible mediators of observed short-term therapeutic effects. The baseline composition of the gut microbiome may influence metformin therapy efficacy and tolerance in T2D patients and could be used as a powerful prediction tool.

Dataset Information

Effect of short-term intensive insulin therapy on ?-cell function in patients with newly diagnosed type 2 diabetes.

Publications

Effect of short-term intensive insulin therapy on α-cell function in patients with newly diagnosed type 2 diabetes.

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