XI. STRATEGIES FOR IMPROVING DIABETES CARE D iabetes is a chronic illness that requires continuing medical care and patient self-management education to prevent acute complications and to reduce the risk of long-term complications. Diabetes care is complex and requires that many issues, beyond glycemic control, be addressed. A large body of evidence exists that supports a range of interventions to improve diabetes outcomes. These standards of care are intended to provide clinicians, patients, researchers, payors, and other interested individuals with the components of diabetes care, treatment goals, and tools to evaluate the quality of care. While individual preferences, comorbidities, and other patient factors may require modification of goals, targets that are desirable for most patients with diabetes are provided. These standards are not intended to preclude more extensive evaluation and management of the patient by other specialists as needed. For more detailed information, refer to Bode (Ed.): Medical Management of Type 1 Diabetes (1), Burant (Ed): Medical Management of Type 2 Diabetes (2), and Klingensmith (Ed): Intensive Diabetes Management (3). The recommendations included are diagnostic and therapeutic actions that are known or believed to favorably affect health outcomes of patients with diabetes. A grading system (Table 1), developed by the American Diabetes Association (ADA) and modeled after existing methods, was utilized to clarify and codify the evidence that forms the basis for the recommendations. The level of evidence that supports each recommendation is listed after each recommendation using the letters A, B, C, or E.

Standards of Medical Care in Diabetes

BackgroundThe cardiovascular effect of liraglutide, a glucagon-like peptide 1 analogue, when added to standard care in patients with type 2 diabetes, remains unknown. MethodsIn this double-blind trial, we randomly assigned patients with type 2 diabetes and high cardiovascular risk to receive liraglutide or placebo. The primary composite outcome in the time-to-event analysis was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The primary hypothesis was that liraglutide would be noninferior to placebo with regard to the primary outcome, with a margin of 1.30 for the upper boundary of the 95% confidence interval of the hazard ratio. No adjustments for multiplicity were performed for the prespecified exploratory outcomes. ResultsA total of 9340 patients underwent randomization. The median follow-up was 3.8 years. The primary outcome occurred in significantly fewer patients in the liraglutide group (608 of 4668 patients [13.0%]) than in the placebo ...

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Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes

Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

BackgroundRegulatory guidance specifies the need to establish cardiovascular safety of new diabetes therapies in patients with type 2 diabetes in order to rule out excess cardiovascular risk. The cardiovascular effects of semaglutide, a glucagon-like peptide 1 analogue with an extended half-life of approximately 1 week, in type 2 diabetes are unknown. MethodsWe randomly assigned 3297 patients with type 2 diabetes who were on a standard-care regimen to receive once-weekly semaglutide (0.5 mg or 1.0 mg) or placebo for 104 weeks. The primary composite outcome was the first occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. We hypothesized that semaglutide would be noninferior to placebo for the primary outcome. The noninferiority margin was 1.8 for the upper boundary of the 95% confidence interval of the hazard ratio. ResultsAt baseline, 2735 of the patients (83.0%) had established cardiovascular disease, chronic kidney disease, or both. The primary outcome occurred in 10...

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Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes.

Obesity and type 2 diabetes are characterized by altered gut microbiota, inflammation, and gut barrier disruption. Microbial composition and the mechanisms of interaction with the host that affect gut barrier function during obesity and type 2 diabetes have not been elucidated. We recently isolated Akkermansia muciniphila, which is a mucin-degrading bacterium that resides in the mucus layer. The presence of this bacterium inversely correlates with body weight in rodents and humans. However, the precise physiological roles played by this bacterium during obesity and metabolic disorders are unknown. This study demonstrated that the abundance of A. muciniphila decreased in obese and type 2 diabetic mice. We also observed that prebiotic feeding normalized A. muciniphila abundance, which correlated with an improved metabolic profile. In addition, we demonstrated that A. muciniphila treatment reversed high-fat diet-induced metabolic disorders, including fat-mass gain, metabolic endotoxemia, adipose tissue inflammation, and insulin resistance. A. muciniphila administration increased the intestinal levels of endocannabinoids that control inflammation, the gut barrier, and gut peptide secretion. Finally, we demonstrated that all these effects required viable A. muciniphila because treatment with heat-killed cells did not improve the metabolic profile or the mucus layer thickness. In summary, this study provides substantial insight into the intricate mechanisms of bacterial (i.e., A. muciniphila) regulation of the cross-talk between the host and gut microbiota. These results also provide a rationale for the development of a treatment that uses this human mucus colonizer for the prevention or treatment of obesity and its associated metabolic disorders.

https://www.pnas.org/content/pnas/110/22/9066.full.pdf

Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity

Human amylin, pramlintide and GLP-1: Influence on gastric emptying, appetite and food intake in humans

The effect of GLP-1 on food intake is lost in trunkally vagotomized subjects

Metformin is an oral anti-hyperglycaemic drug used as first-line treatment of Type 2 diabetes. It is more effective when administered orally than when administered intravenously, and metformin formulations, which prolong the time residing in the gut are the most potent. This indicates that the intestine plays an essential role in metformin's mode of action. Metformin also increases plasma concentrations of the glucose-lowering gut incretin hormone glucagon-like peptide-1 (GLP-1). This metformin-induced GLP-1 increment may constitute an important link between the gut and the glucose-lowering effect of metformin.

[Metformin is a possible glucagon-like peptide 1 stimulator].

The insulinotropic gut hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) are key factors in the regulation of normal postprandial glucose homeostasis, but in most reports, the glucose-lowering effect of GIP has been shown to be blunted or even absent in people with type 2 diabetes (T2D) (1). Despite previous reports that GIP does not potentiate the glucose-lowering effect of GLP-1 in type 2 diabetes (2), a dual GIP/GLP-1 receptor agonist (tirzepatide/LY3298176) has recently been reported to reduce HbA1c and body weight in overweight/obese individuals with type 2 diabetes beyond that of GLP-1 receptor monoagonism (dulaglutide) (3).

Pancreatic polypeptide - a potential biomarker of GIP receptor activation in vivo.

Aims Epidemiological studies show increased occurrence of type 2 diabetes in adults with atopic dermatitis (AD) compared to the general population. We examined whether adults with AD have reduced insulin sensitivity and/or exhibit other gluco-metabolic disturbances that could explain this association. Materials and methods Sixteen adult, non-obese, non-diabetic patients with mild to moderate AD and 16 gender, age and body mass index (BMI)-matched, healthy controls underwent a hyperinsulinemic euglycemic clamp (insulin infusion rate: 40 mU/m2 /min) and an oral glucose tolerance test (OGTT) with frequent blood sampling for gut and pancreatic hormones. Results The two groups were similar in age (33±3 vs. 33±3 years, mean ± standard error of the mean (SEM)), gender (56% women), BMI (24.5±0.7 vs. 24.4±0.7 kg/m2 ), physical activity level, fasting plasma glucose and HbA1c. Patients with AD had a mean Eczema Area and Severity Index score of 8.5±1.0 (moderate disease) and a mean AD duration of 28±3 years. During the OGTT, circulating glucose, insulin, C-peptide, glucagon and glucose-dependent insulinotropic polypeptide, respectively, were similar in the two groups, except glucagon-like peptide-1 which was higher in patients with AD. The clamp showed no differences in insulin sensitivity between groups (M-value 9.2 ± 0.6 vs. 9.8 ± 0.8, P=0.541, 95% CI -1.51;2.60), or circulating insulin, C-peptide and glucagon levels. Conclusions Using OGTT and the hyperinsulinemic euglycemic clamp technique, we found no difference in insulin sensitivity or other gluco-metabolic characteristics between patients with mild to moderate AD and matched healthy controls; suggesting that the inflammatory skin disease AD has little or no influence on glucose metabolism. ClinicalTrials.gov (NCT03003793) This article is protected by copyright. All rights reserved.

Filip K. Knop

Papers

Human amylin, pramlintide and GLP-1: Influence on gastric emptying, appetite and food intake in humans

The effect of GLP-1 on food intake is lost in trunkally vagotomized subjects

[Metformin is a possible glucagon-like peptide 1 stimulator].

Pancreatic polypeptide - a potential biomarker of GIP receptor activation in vivo.

Normal insulin sensitivity, glucose tolerance, gut incretin and pancreatic hormone responses in adults with atopic dermatitis