Incidence Of Diabetes In Subjects Research Articles

The association between the biological disease-modifying anti-rheumatic drugs and the incidence of diabetes: A systematic review and meta-analysis

Whether the use of biological disease-modifying anti-rheumatic drugs (bDMARDs) would influence the risk of new-onset diabetes remains uncertain. Therefore, we performed a systematic review and meta-analysis to evaluate the association between the use of bDMARDs and the incidence of diabetes in patients with systemic inflammatory conditions. Pubmed, Medline, Embase and the Cochrane Central Register of Controlled Trials were searched for studies published from January 2000 to March 2020. Studies conducted in systemic inflammatory conditions with reports of the incidence of diabetes in subjects treated with bDMARDs were included. With 22 randomized controlled trials and 3 cohort studies included, the overall result indicated that compared with non-bDMARD treatment, the use of bDMARDs was significantly associated with decreased incidence of diabetes in patients with systemic inflammatory conditions (RR = 0.56, 95 % CI, 0.43 to 0.74, P < 0.001, I2 = 69 %), especially in patients with in rheumatoid arthritis (RR = 0.54, 95 % CI, 0.38 to 0.76, P = 0.0005, I2 = 26). Reduced risk of new-onset diabetes was observed in studies with follow-up more than 1 year (RR = 0.73, 95 % CI, 0.54 to 0.99, P = 0.04, I2 = 88). New-onset diabetes was less frequent in patients with TNF-α inhibitor treatment (RR = 0.54, 95 % CI, 0.48 to 0.60, P < 0.001, I2 = 42 %) and abatacept treatment (RR = 0.44, 95 % CI, 0.34 to 0.58, P < 0.001, I2 = 3 %), which might be associated with the inhibition of TNF-α mediated inflammatory responses and dysregulated T cell activation and immune responses respectively. Further investigations are required to validate the glucose metabolism protective effect of bDMARDs and clarify the underlying mechanisms of the crosstalk between bDMARDs and diabetes.

275-OR: The Association between the Biological Disease-Modifying Antirheumatic Drugs and Incidence of Diabetes

Purpose: To evaluate the association between the biological disease-modifying anti-rheumatic drugs (bio-DMARDs) and the incidence of diabetes. Methods: Studies recording the incidence of new-onset diabetes in subjects treated with bio-DMARDs were included. Results: In total, 23 relevant studies were included. The pooled analysis suggested that bio-DMARDs treatment did not reduce the incidence of diabetes (RR= 0.87, 95% CI, 0.69 to 1.08, P = 0. 21) compared with non-bioDMARDs. However, subgroup analyses revealed incidence of new-onset diabetes was significantly reduced in patients with abatacept treatment (RR = 0.61, 95% CI, 0.38 to 0.99, P = 0.04). Conclusions: The utilization of bio-DMARDs in general was not associated with the incidence of diabetes while the abatacept treatment may reduce the risk of diabetes. Disclosure C. Lin: None. H. Ji: None. X. Cai: None. W. Yang: None. L. Ji: None. Funding National Natural Science Foundation of China (81970698); National Key Research and Development Program of China (2016YFC1304901)

Risk-benefit analysis of use of statins for primary prevention of cardiovascular disease in subjects without diabetes.

Risk-benefit analysis of use of statins for primary prevention of cardiovascular disease in subjects without diabetes.

Effect of a long‐term oral l‐arginine supplementation on glucose metabolism: a randomized, double‐blind, placebo‐controlled trial

This study assessed the efficacy of long-term l-arginine (l-arg) therapy in preventing or delaying type 2 diabetes mellitus. A mono-centre, randomized, double-blind, parallel-group, placebo-controlled, phase III trial (l-arg trial) was conducted on 144 individuals affected by impaired glucose tolerance (IGT) and metabolic syndrome (MS). l-Arg/placebo was administered (6.4 g/day) on a background structured lifestyle intervention for 18 months plus a 12-month extended follow-up period after study drug termination. Fasting glucose levels and glucose tolerance after oral glucose tolerance test were evaluated throughout the study. After 18 months, l-arg as compared with placebo did not reduce the cumulative incidence of diabetes [21.4 and 20.8%, respectively, hazard ratio (HR), 1.04; 95% confidence interval (CI), 0.58-1.86] while the cumulative probability to become normal glucose tolerant (NGT) increased (42.4 and 22.1%, respectively, HR, 2.60; 95% CI, 1.51-4.46, p < 0.001). The higher cumulative probability to become of NGT was maintained during the extended period in subjects previously treated with l-arg (HR, 3.21; 95% CI, 1.87-5.51; p < 0.001). At the end of the extended period, the cumulative incidence of diabetes in subjects previously treated with l-arg was reduced as compared with placebo (27.2 and 47.1%, respectively, HR, 0.42; 95% CI, 0.24-0.75, p < 0.05). During both periods, l-arg significantly improved insulin sensitivity and β-cell function. Among persons with IGT and MS, the supplementation of l-arg for 18 months does not significantly reduce the incidence of diabetes but does significantly increase regression to NGT.

Central obesity is important but not essential component of the metabolic syndrome for predicting diabetes mellitus in a hypertensive family-based cohort. Results from the Stanford Asia-pacific program for hypertension and insulin resistance (SAPPHIRe) Taiwan follow-up study

BackgroundMetabolic abnormalities have a cumulative effect on development of diabetes, but only central obesity has been defined as the essential criterion of metabolic syndrome (MetS) by the International Diabetes Federation. We hypothesized that central obesity contributes to a higher risk of new-onset diabetes than other metabolic abnormalities in the hypertensive families.MethodsNon-diabetic Chinese were enrolled and MetS components were assessed to establish baseline data in a hypertensive family-based cohort study. Based on medical records and glucose tolerance test (OGTT), the cumulative incidence of diabetes was analyzed in this five-year study by Cox regression models. Contribution of central obesity to development of new-onset diabetes was assessed in subjects with the same number of positive MetS components.ResultsAmong the total of 595 subjects who completed the assessment, 125 (21.0%) developed diabetes. Incidence of diabetes increased in direct proportion to the number of positive MetS components (P ≪ 0.001). Although subjects with central obesity had a higher incidence of diabetes than those without (55.7 vs. 30.0 events/1000 person-years, P ≪ 0.001), the difference became non-significant after adjusting of the number of positive MetS components (hazard ratio = 0.72, 95%CI: 0.45-1.13). Furthermore, in all participants with three positive MetS components, there was no difference in the incidence of diabetes between subjects with and without central obesity (hazard ratio = 1.04, 95%CI: 0.50-2.16).ConclusionIn Chinese hypertensive families, the incidence of diabetes in subjects without central obesity was similar to that in subjects with central obesity when they also had the same number of positive MetS components. We suggest that central obesity is very important, but not the essential component of the metabolic syndrome for predicting of new-onset diabetes. (Trial registration: NCT00260910, ClinicalTrials.gov).

Vitamin D and incidence of diabetes: A prospective cohort study

To investigate the relationship between levels of 25-hydroxyvitamin D and the incidence of type 2 diabetes in a Spanish population. We undertook a population-based prospective study in a population from southern Spain. The first phase of the study (1996-1998) included 1226 individuals. Of this original cohort, 988 persons were reassessed in 2002-2004 and 961 in 2005-2007. Measurements were made of 25-hydroxyvitamin D and intact parathyroid hormone in 2002-2004 and an oral glucose tolerance test was done in three time points. The incidence of diabetes in subjects with 25-hydroxyvitamin D levels ≤ 18.5 ng/mL (percentile 25) was 12.4% vs 4.7% in subjects with levels >18.5 ng/mL. The likelihood of having diabetes during the four years of follow-up was significantly lower in the subjects with higher levels of 25-hydroxyvitamin D [OR = 0.17 (0.05-0.61)]. None of the subjects with levels higher than 30 ng/mL developed diabetes. In this prospective study, we found a significant inverse association between serum 25-hydroxyvitamin D levels and the risk for type 2 diabetes in a population from the south of Spain.

Fasting plasma glucose and HbA1c as risk factors for Type 2 diabetes

We examined the value of combining fasting plasma glucose (FPG) and glycated haemoglobin (HbA(1c)) as a predictor of diabetes, using the new American Diabetes Association (ADA) criteria of FPG and lower cut-off point of HbA(1c). A retrospective cohort study was conducted from 1998 to 2006, inclusive, in 10 042 persons (55 884 person-years), with a mean age of 53.0 years at baseline. The cumulative incidence of diabetes (defined either as an FPG > or = 7.0 mmol/l or as clinically diagnosed diabetes) was measured. The cumulative incidence and incidence density of diabetes were 3.7% (368 cases) and 6.6/1000 person-years over a mean follow-up period of 5.5 years. The cumulative incidence of diabetes in subjects with impaired fasting glucose (IFG) and HbA(1c) 5.5-6.4% was 24.8% (172/694 persons) compared with 0.4% (25/6698 persons), 2.5% (15/605 persons), 7.6% (156/2045 persons) in those with normal fasting glucose (NFG) and HbA(1c) < 5.5%, NFG and HbA(1c) 5.5-6.4% and IFG and HbA(1c) < 5.5%, respectively. The hazard ratio for diabetes, adjusted for possible confounders, was 7.4 (95% confidence interval, 4.70 to 11.74) for those with NFG and HbA(1c) 5.5-6.4%, 14.4 (11.93 to 27.79) for those with IFG and HbA(1c) < 5.5% and 38.4 (24.63 to 59.88) for those with IFG and HbA(1c) 5.5-6.4%. The combination of FPG and HbA(1c) identifies individuals who are at risk of progression to Type 2 diabetes at the new ADA criteria of FPG and a lower cut-off point of HbA(1c) than previous studies.

Effects of pioglitazone and metformin on β-cell function in nondiabetic subjects at high risk for type 2 diabetes

Thiazolidinediones (TZDs) and metformin decreased the incidence of diabetes in subjects at risk for developing diabetes and improved peripheral or hepatic insulin sensitivity, respectively. Whether they also directly improved beta-cell function is not clear. In vitro studies showed improved beta-cell function in response to TZDs and metformin; however, the effects of TZDs or metformin on beta-cell function in humans are still uncertain. We hypothesized that both TZDs and metformin directly affect beta-cell function. We evaluated beta-cell function and insulin sensitivity (S(I)) in subjects with impaired glucose tolerance or a history of gestational diabetes using oral and intravenous glucose tolerance tests in addition to the glucose-potentiated arginine stimulation test. In contrast to metformin, pioglitazone improved S(I), glucose tolerance, and insulin-independent glucose disposal [glucose effectiveness (S(G))]. Neither pioglitazone nor metformin significantly improved beta-cell compensation for insulin resistance [disposition index (DI)], but the change in DI significantly correlated with baseline S(I). Insulin secretion in response to arginine at maximally potentiating glucose levels (AIR(max)) tended to increase after metformin and to decrease after pioglitazone; however, when adjusted for S(I), the changes were not significant. Our results demonstrate that, in nondiabetic subjects at risk for diabetes, pioglitazone, but not metformin, significantly improved glucose tolerance by improving S(I) and S(G). We did not find any evidence that either pioglitazone or metformin improved beta-cell function. Improved beta-cell compensation was observed primarily in the subgroup of subjects that had the lowest S(I) at baseline.

The potential of metformin for diabetes prevention

Well designed intervention trials, such as the Diabetes Prevention Program (DPP), have demonstrated the potential of lifestyle interventions or pharmacologic treatments for the prevention or delay of type 2 diabetes in subjects with impaired glucose tolerance (IGT). Lifestyle interventions are likely to form the cornerstone of the management of IGT in the future, as they do in the management of type 2 diabetes today. However, it remains to be seen whether the intensive lifestyle interventions employed in trials such as the DPP can be transferred successfully from the highly structured environment of a randomised trial to routine, day-to-day management within the primary care sector. Thus, pharmacologic treatment may provide an important additional option where subjects are unwilling or unable to improve their diet and levels of physical activity. Treatment with metformin significantly reduced the incidence of diabetes in subjects with IGT and high-normal fasting plasma glucose in the DPP. Moreover, metformin was well tolerated, and health economic analyses suggest that metformin treatment is cost-effective in the US and Europe. The DPP investigators found that the protective effect of metformin persisted beyond the end of the study, and estimated that only one quarter of the protection arose from a short-lived pharmacological effect. The results of the DPP identify metformin as an effective option for the prevention of diabetes in subjects with IGT and impaired fasting glucose.

Impaired glucose tolerance and metformin: clinical and mechanistic aspects

The Diabetes Prevention Program (DPP) showed that metformin reduced the incidence of diabetes in subjects with impaired glucose tolerance (IGT) who were at high risk of progression to type 2 diabetes. Metformin was not as efficient as intensive life style intervention, but had a clinically significant effect in obese individuals and in those with impaired fasting glucose (IFG). This review discusses the clinical implications and the mechanistic aspects of the effect of metformin in IGT and IFG. Acute actions of metformin on postprandial metabolism to improve hepatic glucose handling and improve the lipid profile could contribute to the lower incidence of diabetes. Longer term improvements in haemodynamic parameters and reduced oxidative stress are also implicated. Metformin offers a potential alternative or complement to lifestyle intervention for IGT, and deserves further evaluation in this respect.