Diabetes mellitus is associated with a considerably increased risk of premature atherosclerotic cardiovascular disease. Intensive glycemic control has essentially failed to significantly improve cardiovascular outcomes in clinical trials. Dyslipidemia is common in diabetes and there is strong evidence that cholesterol lowering improves cardiovascular outcomes, even in patients with apparently unremarkable lipid profiles. Here, the authors review the pathophysiology and implications of the alterations in lipoproteins observed in both type 1 and type 2 diabetes, the effect of medications commonly used in the management of diabetes on the lipid profile, the evidence for lifestyle and pharmaceutical interventions, and national and international recommendations for the management of dyslipidemia in patients with diabetes.

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Diabetes Dyslipidemia

Background
The global prevalence of childhood and adolescent obesity is high. Lifestyle changes towards a healthy diet, increased physical activity and reduced sedentary activities are recommended to prevent and treat obesity. Evidence suggests that changing these health behaviours can benefit cognitive function and school achievement in children and adolescents in general. There are various theoretical mechanisms that suggest that children and adolescents with excessive body fat may benefit particularly from these interventions.

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Physical activity, diet and other behavioural interventions for improving cognition and school achievement in children and adolescents with obesity or overweight.

Metformin is the most widely prescribed drug for patients with type 2 diabetes mellitus and the first-line pharmacological option as supported by multiple international guidelines, yet a rather large proportion of patients cannot tolerate metformin in adequate amounts because of its associated gastrointestinal (GI) adverse events (AEs). GI AEs typically encountered with metformin therapy include diarrhoea, nausea, flatulence, indigestion, vomiting and abdominal discomfort, with diarrhoea and nausea being the most common. Although starting at a low dose and titrating slowly may help prevent some GI AEs associated with metformin, some patients are unable to tolerate metformin at all and it may also be difficult to convince patients to start metformin again after a bout of GI AEs. Despite this clinical importance, the underlying mechanisms of the GI intolerance associated with metformin are poorly known. In the present review, we discuss: the epidemiology of metformin-associated GI intolerance and its underlying mechanisms; genotype variability and associated factors affecting metformin GI intolerance, such as comorbidities, co-medications and bariatric surgery; clinical consequences and therapeutic strategies to overcome metformin GI intolerance. These strategies include appropriate titration of immediate-release metformin, use of extended-release metformin, the promise of delayed-release metformin and gut microbiome modulators, as well as alternative pharmacological therapies when metformin cannot be tolerated at all. Given the available data, all efforts should be made to maintain metformin before considering a shift to another drug therapy.

Understanding and overcoming metformin gastrointestinal intolerance.

https://www.thelancet.com/pdfs/journals/landia/PIIS2213-8587(15)00462-3.pdf

Future glucose-lowering drugs for type 2 diabetes.

Obesity and chronic pain: systematic review of prevalence and implications for pain practice.

Introduction
Combining antihyperglycemic agents with complementary mechanisms of action is a cornerstone of type 2 diabetes mellitus (T2DM) management. Although several fixed-dose combinations (FDCs) are available, representing standard types of combination therapy in T2DM, use of these products has been limited.

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Fixed-Dose Combinations for Treatment of Type 2 Diabetes Mellitus

Background: Cardiovascular disease is the leading cause of morbidity and mortality among patients with diabetes, underscoring the importance of choosing drugs that do not increase cardiovascular risk and reduce the risk of cardiovascular events. Since 2008, the US Food and Drug Administration has recommended that new drugs for type 2 diabetes undergo clinical trials to demonstrate cardiovascular safety in addition to glycemic benefit. In 2012, the European Medicines Agency issued a similar recommendation. Methods: We searched the PubMed, Cochrane CENTRAL, EMBASE, and CINAHL databases from inception through August 2013 and compiled and reviewed the existing data on the cardiovascular safety profiles of currently available diabetic drugs. Results: While intensive glycemic control in diabetics has been consistently shown to reduce the risk of microvascular complications, the data on macrovascular risk reduction have not been as clear, and questions have been raised about possible increases in cardio...

Cardiovascular safety profile of currently available diabetic drugs.

Fixed-dose combination therapy in type 2 diabetes mellitus.

Diabetes mellitus is a chronic systemic disease with multiple complications ranging from microvascular to macrovascular diseases. Type 1 diabetes comprises 5 % of adults with diabetes in the US. This population is shown to be at increased risk of cardiovascular events and mortality. Intensive glycemic control has been consistently associated with decreased microvascular complications but trials on macrovascular benefit yielded mixed results over the years. Recent data from long-term observational follow-up studies of major diabetes cardiovascular events and mortality are showing benefits that were not seen with the initial interventional trials. This article will review evidence on the effect of glycemic control on complications in diabetes mellitus with a focus on cardiovascular mortality in type 1 diabetes.

Glycemic Control and Excess Cardiovascular Mortality in Type 1 Diabetes

Obesity, classified by the American Medical Association in 2013 as a disease, is an epidemic that is drawing serious global attention. It is the most common preventable disease and the most common modifiable risk factor for several chronic diseases. It is an independent cause of increased morbidity and mortality. Obesity is spreading across most countries, socio-economic strata, age groups, gender groups, and races, albeit to variable degrees. It is concerning that both adults and children are increasingly afflicted by obesity. Both incidence and prevalence of the disease are on the rise. The direct and indirect costs attributable to obesity have reached billions of US dollars. Obesity management involves a multi-disciplinary approach that includes the patient and his or her family, the primary care provider, a dietician or nutrition specialist and physical trainer. It may also require specialist care in the use of pharmacological and surgical interventions. Currently available anti-obesity drugs are indicated for those who are obese (BMI of 30 kg/m(2)) or overweight (BMI of 27 kg/m(2)) with at least one weight-related comorbid condition. This article focuses on the FDA-approved antiobesity drugs, their mechanisms of action, chemical structures, efficacy, safety profiles and known side effects.

Zinnia T. San Juan

Papers

Fixed-Dose Combinations for Treatment of Type 2 Diabetes Mellitus

Cardiovascular safety profile of currently available diabetic drugs.

Fixed-dose combination therapy in type 2 diabetes mellitus.

Glycemic Control and Excess Cardiovascular Mortality in Type 1 Diabetes

Contemporary review of drugs used to treat obesity.