COVID-19-Induced Diabetic Ketoacidosis in an Adult with Latent Autoimmune Diabetes.

Latent autoimmune diabetes in adults (LADA) is a type of slow-onset, immune-mediated insulin deficiency involving progressive destruction of beta-cell function. Despite sharing some similarities with both type 1 and type 2 diabetes, LADA is a separate entity that should be given equal attention as patients with this condition are subject to severe complications and preventable hospitalizations without proper medical management if not diagnosed in a timely manner. Herein, we describe the case of a 45-year-old Hispanic female with a past medical history of presumed noninsulin-dependent type 2 diabetes managed with metformin for six years who presented with fatigue, dry cough, and intermittent presyncope for one week. Laboratory data revealed evidence of diabetic ketoacidosis. She also tested positive for coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although her respiratory status was stable and did not require treatment for COVID-19, she required high doses of insulin to normalize hyperglycemia and spent two days in the intensive care unit (ICU). Further evaluation revealed positive islet autoantibodies and decreased C-peptide levels, leading to a diagnosis of LADA. SARS-CoV-2 has been shown to enter islet cells via the angiotensin-converting enzyme-2 (ACE2), causing damage and inducing acute diabetes and associated complications, including ketoacidosis. It is conceivable that this patient had acute worsening of her diabetes through this mechanism. Recognition of this association may contribute to the timely diagnosis of LADA and prevention of medical complications due to inappropriate diabetes therapy.

Comparison of extended release GLP-1 receptor agonist therapy versus sitagliptin in the management of type 2 diabetes.

Exenatide once weekly (EQW), the first glucose-lowering agent for type 2 diabetes that is dosed one time per week, contains exenatide encapsulated in microspheres of a dissolvable matrix, which release active agent slowly and continuously into the circulation following subcutaneous injection. In two direct head-to-head comparisons, EQW resulted in better long-term glucose control, greater reductions in fasting plasma glucose, and more significant weight loss than sitagliptin. In other trials, glucose-lowering effects of EQW compared favorably with those of metformin, pioglitazone, and basal insulin. Patients on EQW exhibited a higher incidence of nausea than those on sitagliptin, although gastrointestinal adverse events occurred primarily during the first 6-8 weeks of therapy and declined thereafter. EQW was also associated with a lower incidence of nausea than two other glucagon-like peptide-1 receptor agonists, exenatide twice daily and liraglutide. Mild hypoglycemic episodes were uncommon with EQW, although risk of hypoglycemia increased in combination with sulfonylureas. When choosing between EQW and a dipeptidyl peptidase-4 (DPP-4) inhibitor, such as sitagliptin, clinicians and patients should consider the differences between the two medications in terms of glucose control (EQW superior to DPP-4 inhibitors), weight control (EQW superior to DPP-4 inhibitors), gastrointestinal tolerability during treatment initiation (EQW inferior to DPP-4 inhibitors), and mode of administration (once-weekly subcutaneous administration versus once-daily oral administration).

Addressing cardiovascular risk in patients with type 2 diabetes: focus on primary care.

Type 2 diabetes is a disorder of glucose and lipid metabolism associated with increased risk of macrovascular and microvascular complications. The primary focus of treating type 2 diabetes is glycemic control; simultaneous management of cardiometabolic risk factors, including blood pressure, lipid profile and overweight/obesity, has been shown to improve outcomes. All patients with diabetes require individualized combination therapy including diet and exercise intervention to help prevent microvascular and macrovascular complications. Because primary care physicians in the United States provide the majority of care for patients with type 2 diabetes, this article discusses the management of cardiovascular risk with a specific focus on primary care. In addition, mechanisms by which existing and novel antidiabetes therapies may modulate the metabolic pathways and a review of the benefits of cardiovascular risk reduction using multifactorial, primary care-focused intervention strategies will be discussed. Finally, early- and late-stage disease management strategies are discussed.

Defining and achieving treatment success in patients with type 2 diabetes mellitus.

Traditionally, successful treatment of patients with type 2 diabetes mellitus (DM) has been defined strictly by achievement of targeted glycemic control, primarily using a stepped-care approach that begins with changes in lifestyle combined with oral therapy that is slowly intensified as disease progression advances and ß-cell function declines. However, stepped care is often adjusted without regard to the mechanism of hyperglycemia or without long-term objectives. A more comprehensive definition of treatment success in patients with type 2 DM should include slowing or stopping disease progression and optimizing the reduction of all risk factors associated with microvascular and macrovascular disease complications. To achieve these broader goals, it is important to diagnose diabetes earlier in the disease course and to consider use of more aggressive combination therapy much earlier with agents that have the potential to slow or halt the progressive ß-cell dysfunction and loss characteristic of type 2 DM. A new paradigm for managing patients with type 2 DM should address the concomitant risk factors and morbidities of obesity, hypertension, and dyslipidemia with equal or occasionally even greater aggressiveness than for hyperglycemia. The use of antidiabetes agents that may favorably address cardiovascular risk factors should be considered more strongly in treatment algorithms, although no pharmacological therapy is likely to be ultimately successful without concomitant synergistic lifestyle changes. Newer incretin-based therapies, such as glucagon-like peptide 1 receptor agonists and dipeptidyl peptidase 4 inhibitors, which appear to have a favorable cardiovascular safety profile as well as the mechanistic possibility for a favorable cardiovascular risk impact, are suitable for earlier inclusion as part of combination regimens aimed at achieving comprehensive treatment success in patients with type 2 DM.

Improving outcomes in patients with type 2 diabetes mellitus: practical solutions for clinical challenges.

The incidence and prevalence of type 2 diabetes mellitus (T2DM) in the United States continue to rise, and the disease has become an enormous health concern. While effective glycemic management reduces the risk of diabetes-related complications in patients with T2DM, many patients are unable to reduce their glucose levels to target goals. The authors review key elements in the management of T2DM with an emphasis on achieving and maintaining glycemic control. Strategies are offered to provide practical solutions to the challenges faced by healthcare providers and patients with T2DM. The importance of implementing evidence-based practice guidelines while empowering patients to participate in self-management of their disease is highlighted.

Glycemic control and complications in type 2 diabetes mellitus.

Current guidelines for treating patients with type 2 diabetes mellitus are based on glycemic standards derived from epidemiologic data; however, the course of the disease, from prediabetes to end-stage complications, is not the same in all patients. Microvascular complications, including nephropathy, retinopathy, and neuropathy, are strongly related to hemoglobin A1c (HbA1c). However, vascular complications may progress in patients who have HbA1c <7.0% and may appear even in undiagnosed patients owing to transient increases in plasma glucose concentrations. Concomitant atherosclerosis and occult macrovascular disease may follow an accelerated course in type 2 diabetes. Macrovascular complications may develop early, and, like microvascular complications, do not correlate linearly with HbA1c. Managing hyperglycemia in the later stages of type 2 diabetes does not appear to be associated with improved cardiovascular outcomes. The glucotoxicity and lipotoxicity that may precede prolonged hyperglycemia and beta-cell dysfunction are early, reversible pathophysiologic events. This suggests that prompt management may modify the course of hyperglycemia and prevent or delay long-term complications. The challenge remains to identify patients with early type 2 diabetes who are at risk for rapid progression of beta-cell decline and premature development of microvascular complications. Ongoing research into the mechanisms responsible for diabetic complications may provide new markers to help identify patients with type 2 diabetes who can benefit from earlier antidiabetes treatments.

Managing type 2 diabetes: going beyond glycemic control.

BACKGROUND: Aggressive management of type 2 diabetes is necessary to achieve glycemic and nonglycemic treatment goals. Attainment of treatment goals is associated with a decreased risk of diabetes-related complications, costs, and health care utilization. OBJECTIVE: To review the advantages and disadvantages of different glucose-lowering agents, with an emphasis on the role of thiazolidinediones (TZDs). SUMMARY: Diabetes has become increasingly prevalent, particularly among younger age groups in the United States, accounting for approximately 15% of health care expenditures by managed care organizations. Reducing a patient's glycated hemoglobin (A1C) has been shown to decrease the risk of diabetes-related complications, as well as reduce medical costs and health care utilization. Despite this knowledge, achievement of the American Diabetes Association (ADA) goal A1C of < 7% is suboptimal, and < 1 in 10 patients also reach the ADA targets for cholesterol (low-density lipoprotein < 100 mg per dL) and blood pressure (< 130/80 mm Hg). To ensure that all ADA treatment goals are met, clinicians need to closely monitor patients and adjust therapy as needed, taking into consideration both a drug's glycemic and nonglycemic effects when selecting medication therapy. Four basic defects contribute to type 2 diabetes: insulin resistance, decreased insulin secretion, increased hepatic glucose production, and reduced glucagon-like peptide-1 levels. Unlike metformin, sulfonylureas, and insulin that address only 1 or 2 physiologic defects, TZDs uniquely address 3 of these defects at the adipocyte. Metformin is recommended for initial drug therapy; TZDs, sulfonylureas, and insulin are useful options as add-on therapy for patients whose A1C levels remain >or= 7% despite treatment with metformin and lifestyle interventions. It has been suggested that TZDs, when used either as add-on therapy or when appropriate as monotherapy, may conserve pancreatic beta-cell function over an observed 3- to 5-year period of time and sustain a decrease in A1C ranging from 0.5%-1.5%. Although rarely associated with hypoglycemia, TZDs may cause total body weight gain that is most commonly caused by volume expansion, which may manifest as new or worsened heart failure in susceptible individuals. Pioglitazone and rosiglitazone, the 2 TZDs available in the United States, contain black box label warnings about their potential to cause or exacerbate congestive heart failure; additional data have suggested a link to ischemic cardiac events. Recent data also suggest that TZDs may reduce bone density. Conversely, pioglitazone may have some vasculoprotective effect related to elevation of high-density lipoprotein and lessened progression of carotid intima-media thickness; however, any effect on macrovascular clinical outcomes is unknown. Other drug options are available for the treatment of type 2 diabetes, such as incretin-based therapies. Yet despite their favorable effects on glycemia, they have not been included to date in the ADA treatment algorithm. CONCLUSIONS: Proper glycemic control and attainment of other nonglycemic management targets (e.g., blood pressure, lipids, body weight) are essential to the prevention of long-term complications of diabetes and to reduction of overall disease management costs. Therefore, patients with diabetes should be followed closely to ensure that they achieve and maintain both glycemic and nonglycemic treatment goals. Most patients will not sustain an adequate level of control using nondrug or single-drug therapeutic approaches. When choosing among treatment options, consideration should be given to the nonglycemic as well as glycemic effects of various glucose-lowering agents.

Metabolic syndrome: controversial but useful.

The metabolic syndrome--the cluster of obesity, impaired fasting glucose, elevated triglycerides, low high-density lipoprotein cholesterol, and hypertension--may not be a "real" syndrome in the strict sense. It can, however, still be a useful concept if it prompts a physician to look for and treat additional risk factors when a patient is found to have one risk factor, or if it helps persuade patients to undertake healthy lifestyle changes before they develop overt diabetes mellitus or coronary artery disease.

Type 2 diabetes, cardiovascular risk, and the link to insulin resistance.

BACKGROUND: Patients with type 2 diabetes mellitus frequently have coexistent dyslipidemia, hypertension, and obesity, and are at risk for microvascular and macrovascular disease complications such as myocardial infarction, stroke, retinopathy, and microalbuminuria. To optimize cardiovascular health outcomes for patients with type 2 diabetes, strategies to reduce the risks of microvascular and macrovascular disease are needed in clinical practice. OBJECTIVE: This article provides an overview of the cardiovascular risk profile of patients with type 2 diabetes and discusses the cardiovascular consequences of use of the thiazolidinediones (insulin-sensitizing agents) in the treatment of type 2 diabetes. METHODS: A literature search of MEDLINE/PubMed was performed to identify relevant articles published from 1966 to April 2003. Search terms used were diabetes, cardiovascular disease, atherosclerosis, dyslipidemia, obesity, hypertension, blood pressure, hyperglycemia, inflammation, C-reactive protein, fibrinolysis, plasminogen activator inhibitor type-1, microalbuminuria, thiazolidinediones, safety, hepatotoxicity, and edema. Bibliographies within the identified articles were also evaluated for additional relevant articles and information. RESULTS: Recommendations for cardiovascular risk reduction through preventive and therapeutic strategies that target the symptoms of insulin resistance may reduce the microvascular and macrovascular sequelae of diabetes and ameliorate the impact of other components of the metabolic syndrome, including hypertension, hyperglycemia, and obesity. In this regard, thiazolidinediones are promising therapies. CONCLUSIONS: Early data suggest that, in addition to reducing hyperglycemia, pioglitazone and rosiglitazone effect changes in the dyslipidemic profile, hemodynamics, vascular inflammation, and endothelial functioning of patients with type 2 diabetes. Additional research is needed to further distinguish the cardiovascular benefits of these drugs.

Insulin resistance, diabetes, and the adipocyte.

The etiology, natural history, and relationship of insulin resistance to type 2 diabetes mellitus and the effects of insulin-sensitizing agents are described. Insulin resistance results from a combination of genetic and environmental factors and contributes to type 2 diabetes mellitus, dyslipidemia, hypertension, central (abdominal) obesity, and cardiovascular disease. Insulin resistance does not necessarily progress to impaired glucose tolerance or diabetes because insulin secretion by normal pancreatic beta cells can increase to compensate for reduced physiological activity. Diabetes may develop in insulin-resistant persons with inherited secretory and glucose-sensing defects in beta cells. The pathogenesis of diabetes appears to involve a progressive decrease in beta-cell mass, potentially triggered by abnormalities in adipocytokine release from intraabdominal fat cells. Metformin and the thiazolidinediones are used to treat insulin resistance, but their actions differ. Metformin reduces free-fatty-acid efflux from fat cells, thereby suppressing hepatic glucose production, and indirectly improves peripheral insulin sensitivity and endothelial function. Thiazolidinediones improve peripheral insulin sensitivity by reducing circulating free fatty acids but also by suppressing adipocytokines, which increase insulin resistance. Thiazolidinediones also improve endothelial function and may prevent or delay the onset of diabetes. Insulin is intrinsically antiatherogenic but may mediate arterial inflammation in insulin-resistant patients. Unlike metformin, the thiazolidinediones suppress this inflammatory pathway and may indirectly help preserve beta-cell function. Insulin resistance, resulting from a combination of genetic and environmental factors, plays a central role in type 2 diabetes mellitus. Diabetes may develop in insulin-resistant persons with inherited secretory and glucose-sensing defects in beta cells. Metformin and thiazolidinediones are insulin-sensitizing agents with different mechanisms of action and effects in patients with type 2 diabetes mellitus.