The Influence of Age, Sex, and Socioeconomic Status on Glycemic Control Among People with Type 1 and Type 2 Diabetes in Canada: A Patient-Led Longitudinal Retrospective Cohort Study

Background: Clinical guidelines for most adults with diabetes recommend maintaining hemoglobin A1c (HbA1c) ≤7.0% (≤53 mmol/mol) to avoid microvascular and macrovascular complications. People with diabetes of different ages, sexes, and socioeconomic statuses may differ in their ease of attaining this goal. As a team of people with diabetes, researchers, and health professionals, we aimed to explore patterns in HbA1c results among people with type 1 or type 2 diabetes in Canada. Our research question was identified by people living with diabetes. Methods: We used generalized estimating equations to analyze the effects of age, sex and socioeconomic status in 947,543 HbA1c results measured from 2010 to 2019 among 90,770 people living with type 1 or 2 diabetes in Canada. People living with diabetes reviewed and interpreted the results. Results: HbA1c results at or below 7.0% represented 30.5% (male people living with type 1 diabetes), 21.0% (female people living with type 1 diabetes), 55.0% (male people living with type 2 diabetes) and 59.0% (female people living with type 2 diabetes) of results in each subcategory. We observed higher HbA1c values during adolescence and, for people living with type 2 diabetes, among people living in lower income areas. Among those with type 1 diabetes, female people tended to have lower HbA1c than male people during childbearing years but higher HbA1c than male people during menopausal years. Team members living with diabetes confirmed that the patterns we observed reflected their own life courses and suggested these results be communicated to health professionals and other stakeholders to improve treatment for people living with diabetes. Conclusions: A substantial proportion of people with diabetes in Canada are insufficiently supported to maintain guideline-recommended glycemic control goals. Blood sugar management goals may be particularly challenging for people who are going through adolescence, menopause, or living with fewer financial resources. Health professionals should be aware of the challenging nature of glycemic management and policymakers in Canada should provide more support for people with diabetes to live healthy lives.

Vitamin D Deficiency in Patients with Diabetes in French Guiana: Epidemiology and Relation with Microvascular and Macrovascular Complications

Vitamin D (VD) insufficiency is common among patients with diabetes in French Guiana. The study aimed to evaluate the prevalence of VD deficiency in the different type of diabetes encountered and to analyze the relationship between VD deficiency and diabetes complications. Methods: An observational study was conducted between May 2019 and May 2020 in French Guiana, based on data from the CODIAM study (Diabetes Cohort in French Amazonia), describing the characteristics of patients with diabetes mellitus. Among 600 patients enrolled with diabetes, 361 had an available VD assay. Results: The mean 25(OH)VD (hydroxycalciferol) level was 27.9 ng/mL. The level of VD was inversely proportional to the HbA1c (glycated hemoglobin) level. Patients with angina pectoris had a greater proportion of deficiencies VD < 20 ng/mL than those without angina. By contrast, patients with retinopathy had higher vitamin D concentrations than those without retinopathy. There was no association between vitamin D and arteriopathy, stroke, nephropathy and polyneuropathy. VD deficiency was more frequent in women, and in patients with a high school education. Conclusion: The prevalence of VD deficiency was high in patients with diabetes in French Guiana, emphasizing the importance of VD supplementation.

Mechanisms of Action of Flavonoids in the Management of Diabetes mellitus

Management of diabetes mellitus is a challenge for clinicians. Uncontrolled hyperglycemia increases the risk of microvascular and macrovascular complications, damaging the body systems. Although a number of antidiabetic drugs are available for therapeutic intervention, toxicity, loss of efficacy in chronic use and high cost of treatment have necessitated the search for new molecules to manage diabetes. Safety and cost are the main prerequisite for the new antidiabetic molecules. Medicinal plants and their purified phytochemicals have shown promising antidiabetic potential in the past few years. The flavonoids can be widely classified into different categories like anthocyanins, catechins, flavanols, flavones, flavanones etc. Some flavonoids have hypoglycemic properties. They may improve al-tered glucose and oxidative metabolisms of diabetic states. The hypoglycemic effect of some herbal extracts has been confirmed in human and animal models of type 2 diabetes mellitus (T2DM). Some of the important phytoconstituents from the classes of flavonoid have been discussed here. The current review summarizes the antidiabetic activity of flavonoids, the mechanism-based action of flavonoids that target the various metabolic pathways in humans. Keywords: Diabetes mellitus, Flavonoids, Medicinal plants, mechanisms of action, T2DM

Selective Autophagy in Hyperglycemia-Induced Microvascular and Macrovascular Diseases

Dysregulation of autophagy is an important underlying cause in the onset and progression of many metabolic diseases, including diabetes. Studies in animal models and humans show that impairment in the removal and the recycling of organelles, in particular, contributes to cellular damage, functional failure, and the onset of metabolic diseases. Interestingly, in certain contexts, inhibition of autophagy can be protective. While the inability to upregulate autophagy can play a critical role in the development of diseases, excessive autophagy can also be detrimental, making autophagy an intricately regulated process, the altering of which can adversely affect organismal health. Autophagy is indispensable for maintaining normal cardiac and vascular structure and function. Patients with diabetes are at a higher risk of developing and dying from vascular complications. Autophagy dysregulation is associated with the development of heart failure, many forms of cardiomyopathy, atherosclerosis, myocardial infarction, and microvascular complications in diabetic patients. Here, we review the recent findings on selective autophagy in hyperglycemia and diabetes-associated microvascular and macrovascular complications.

Glucose Variability: How Does It Work?

A growing body of evidence points to the role of glucose variability (GV) in the development of the microvascular and macrovascular complications of diabetes. In this review, we summarize data on GV-induced biochemical, cellular and molecular events involved in the pathogenesis of diabetic complications. Current data indicate that the deteriorating effect of GV on target organs can be realized through oxidative stress, glycation, chronic low-grade inflammation, endothelial dysfunction, platelet activation, impaired angiogenesis and renal fibrosis. The effects of GV on oxidative stress, inflammation, endothelial dysfunction and hypercoagulability could be aggravated by hypoglycemia, associated with high GV. Oscillating hyperglycemia contributes to beta cell dysfunction, which leads to a further increase in GV and completes the vicious circle. In cells, the GV-induced cytotoxic effect includes mitochondrial dysfunction, endoplasmic reticulum stress and disturbances in autophagic flux, which are accompanied by reduced viability, activation of apoptosis and abnormalities in cell proliferation. These effects are realized through the up- and down-regulation of a large number of genes and the activity of signaling pathways such as PI3K/Akt, NF-κB, MAPK (ERK), JNK and TGF-β/Smad. Epigenetic modifications mediate the postponed effects of glucose fluctuations. The multiple deteriorative effects of GV provide further support for considering it as a therapeutic target in diabetes.

Salivary gland proteins alterations in the diabetic milieu

Salivary glands are considered the chief exocrine glands of the mouth and physiologically contribute to the maintenance of the homeostasis of the oral cavity. They consist of the parotid, submandibular and sublingual glands, which come in pairs and are collectively called the major glands, and the minor glands, which are much smaller and are dispersed throughout the buccal cavity. Salivary glands are distinguished by their size, amount of saliva secretion and their location in the oral cavity. Salivary glands pathophysiology has been a subject of interest in various worldwide metabolic disorders, including diabetes mellitus. Diabetes mellitus (DM), a global health concern, with a pathological imprint involved in vasculature, promotes microvascular and macrovascular complications among which periodontitis ranks sixth. Indeed, DM has also been directly associated with oral health lesions. Specifically, salivary glands in the context of diabetes have been a focal point of study and emphasis in the research field. There is evidence that relates salivary secretion content and diabetes progression. In this review, we present all the reported evidence of the deregulation of specific salivary proteins associated with the progression of diabetes in parallel with changes in salivary gland morphology, cellular architecture, and salivary secretion and composition more generally.

Diabetes and the kidney

Diabetic renal disease is the commonest cause of end-stage renal disease (ESRD) in the Western world and is rapidly becoming the leading cause in developing countries. The following chapters provide valuable insights into the epidemiology, pathophysiology, and pathology of diabetic renal disease with a focus on the clinical presentation, diagnosis, natural history, and progression of the disease. Many patients with diabetic renal disease suffer from microvascular and macrovascular complications of diabetes, including diabetic retinopathy, neuropathy, cardiovascular, and peripheral vascular disease. The authors discuss the available treatment approaches including lifestyle, diet, and exercise. In addition, they cover the importance of maintaining healthy blood pressure and glycaemic control to improve outcomes and the pharmacological treatments available. The authors describe the range of hypoglycaemic agents now available as well as insulin treatment. Ultimately, many patients will require management of complications of diabetes. Often they develop progressive renal impairment that requires renal replacement therapy with dialysis and transplantation, which are also discussed.

Hypoglycemia and the risk of cardiovascular complications in patients with type 2 diabetes mellitus. The importance of glycemic control

Diabetes mellitus remains a global medical and social challenge partly because of microvascular and macrovascular complications resulting from hypo- and hyperglycemia. Medical practitioners must be aware of pathophysiological mechanisms underlying the diabetes-related adverse events in patients of various ages, as well as of the disease control options. Therefore, teaching the diabetic patients to self-monitor blood glucose is important.