Chronicle of Diabetes Research and Practice

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Background: Diabetic foot wound is an important health challenge throughout the world. Interleukin 8 (IL8) and macrophage-migration inhibitory factor (MIF) play a significant role in host defense and in wound healing. Immune perturbation and Vitamin D deficiency also contribute to nonhealing of diabetic foot wounds. We aimed to evaluate the serum concentration of IL8 and MIF in diabetic patients with and without foot infection and its association with Vitamin D status. Material and Methods: Serum concentrations of 25 dihydroxyvitamin Vitamin D and cytokines (IL8 and MIF) were measured by radioimmunoassay and enzyme-linked immunosorbent assay, respectively, from 100 subjects with diabetes and foot infection as cases and 73 subjects with diabetes without foot infection as controls. Data were presented as mean (± standard error of mean [SE]) unless otherwise indicated and were analyzed by SPSS 16.0. Results: There was no significant difference in the mean (±SE) of age, duration of diabetes, hemoglobin A1C, and body mass index between the two groups. The mean (±SE) concentration of IL8 was significantly higher and MIF was significantly lower in cases than controls. Vitamin D correlated negatively with IL8 (r = −0.191) and positively (r = 0.1) with MIF. However, only the former correlation was statistically significant (P = 0.01). IL8 was also significantly high in patients with severe Vitamin D deficiency (<10 ng/ml) compared to patients with Vitamin D more than 10 ng/ml. Conclusion: Serum concentration of IL8 is significantly higher in diabetic foot infections compared to controls. Severe Vitamin D deficiency was associated with IL8 concentration in patients with diabetes.

Background: Hyperglycemia is a known risk factor for diabetic retinopathy (DR) but the association between glycemic variability and DR is unclear. We aim to evaluate the glycemic variability in DR through retrospective continuous glucose monitoring (CGM) and assess its effect on the clinical profile of participants with or without DR. Material and Methods: Retrospective observational hospital-based case-control study. We collected anthropometric and clinical data of 74 people with type 2 diabetes from our ophthalmology database whose retrospective CGM data were available. Among them, 37 had DR (cases) and 37 did not have DR (controls). The data were analyzed using SPSS version 27. Results: Duration of diabetes and glycosylated hemoglobin (HbA1c) was significantly higher and the estimated glomerular filtration rate (eGFR) was significantly lower in the cases compared to the controls. CGM markers, like time-above-range, average glucose, glucose management indicator, were higher while time-in-range was lower in the cases compared to the controls (P = ns). Time-below-range targets in people >65 years were met in a lower proportion (p < 0.05) of people in the cases (50%) compared to the controls (92%). Conclusion: Duration of diabetes, low eGFR, and high HbA1c showed significant association with retinopathy in type 2 diabetes. Although markers of glycemic variability did not show a statistically significant difference in cases compared to controls, all indices of glycemic variability were numerically higher in people with DR. Hypoglycemia in elderly participants with DR and its implications on achieving targets requires more research.

Background: Insulin resistance (IR) is commonly seen in diabetic kidney disease (DKD) and could contribute to the progression of renal disease and cardiovascular risk. In this study, we aim to measure homeostasis model assessment IR (HOMA-IR) in DKD and see the effect of advancing kidney disease on HOMA IR. Material and Methods: We recruited 120 subjects with type 2 diabetes mellitus and divided them into people without kidney disease (controls; n = 20), early DKD (n = 40), and advanced DKD (n = 60). Biochemical tests including fasting plasma glucose and fasting serum C-peptide were done in 120 subjects. IR was calculated by the HOMA model in 109 subjects. Data were presented as median (interquartile range [IQR]). Univariable and multivariable analysis was done. Results: Median of HOMA-IR in the control group was 2.0 (IQR: 1.5–2.8; n = 20), early DKD group was 2.3 (1.8–2.9; n = 37), and advanced DKD group was 3.67 (1.6–3.9; n = 52). P = 0.03 indicated a significant increase in the HOMA IR with advancing kidney disease. Conclusion: In patients with DKD, with advancing kidney disease, there was a significant increase in the HOMA IR, a marker of IR. IR is a modifiable metabolic risk factor, and if it is managed by novel therapeutic ways, it might improve clinical outcomes in DKD.

The prevalence of gestational diabetes mellitus (GDM) has been increasing globally and in India too, because of urbanization and the increasing occurrence of obesity. The management of GDM poses a clinical challenge, and this article focuses on its diagnosis and treatment. In India, screening of all pregnant women is recommended at the first antenatal visit and then repeat screening at 24–28 weeks of gestation if the initial screen is normal. Early intervention with counseling, glucose monitoring, diet, and exercise to achieve good glucose control could reduce both the maternal and fetal complications associated with hyperglycemia in pregnancy. The majority of cases of GDM may be managed by lifestyle modifications alone. Metformin may be prescribed as an alternative to insulin as per certain guidelines, though insulin remains the cornerstone of pharmacotherapy. Long-acting insulin detemir and short-acting insulin analogs such as insulin lispro or aspart are safe in pregnancy and help with control of blood glucose. Good glycemic control, achieved by lifestyle measures, monitoring, and medications when needed, may help achieve the goal of a successful pregnancy outcome.

Adenosine Mono phosphate -activated protein kinase (AMPK) is a metabolic master switch that senses the cellular AMP levels. However, it is now also regarded as a nutrient-sensing enzyme due to its ability to detect glucose deprivation inside the cell. Under conditions of energy deprivation, AMPK is activated, which in turn switches on all the energy-producing metabolic pathways, while switching off energy-consuming metabolic pathways and cellular processes. There is a growing interest in AMPK due to its role in a wide array of pathological processes including diabetes mellitus. It is the therapeutic target of one of the most commonly prescribed classes of antidiabetic drugs, namely the biguanides such as metformin. The current article presents a review of AMPK structure, triggers, and mechanisms of its activation as well as its role in cell metabolism, mitochondrial homeostasis, autophagy, and cell proliferation. It also briefly addresses the relevance of AMPK to pathogenesis and management of diabetes mellitus.

Diabetes is considered as a risk factor for the severity of coronavirus disease 2019 (COVID-19). The mortality rate of COVID-19 was found to be high among patients with diabetes. The exact molecular mechanism involved in diabetes-associated COVID-19 severity is not established. In this review, we discuss the exacerbated formation of advanced glycation end products (AGEs), AGE-receptor for AGE (RAGE) signaling induced spike in inflammatory cytokines, and the role of metformin, an antidiabetic drug with glycation inhibition property. The commonality between these two diseases is exacerbated immune response. AGEs interact with RAGE, leading to oxidative stress, activation of the pro-inflammatory pathway, and production of inflammatory cytokines, which may aberrantly activate the immune response. Based on these pieces of evidence, we propose a role for glycation in the pathogenesis of COVID-19 severity.

Online since 15^th October 2021