Heart failure (HF) is an important comorbidity in individuals with diabetes. Most commonly, the condition is secondary to ischaemia and hypertension. Diabetic cardiomyopathy is becoming increasingly ...recognised as a cause of HF and blood glucose control plays a pivotal role in the prevention and treatment of HF. Since the US Food and Drug Administration regulatory guidance in 2008, new glucose-lowering agents are evaluated routinely by cardiovascular outcome trials. These trials offer a wealth of knowledge and allow better understanding of the risks and benefits of contemporary diabetes medications. In this review, we will focus on the risks of HF with emerging glucose-lowering therapies and the safety of these medications in patients with established HF. We will summarise the guidance that is available for the treatment algorithm of diabetes in those with HF and highlight future areas of research.
Metabolomic profiling of obese versus lean humans reveals a branched-chain amino acid (BCAA)-related metabolite signature that is suggestive of increased catabolism of BCAA and correlated with ...insulin resistance. To test its impact on metabolic homeostasis, we fed rats on high-fat (HF), HF with supplemented BCAA (HF/BCAA), or standard chow (SC) diets. Despite having reduced food intake and a low rate of weight gain equivalent to the SC group, HF/BCAA rats were as insulin resistant as HF rats. Pair-feeding of HF diet to match the HF/BCAA animals or BCAA addition to SC diet did not cause insulin resistance. Insulin resistance induced by HF/BCAA feeding was accompanied by chronic phosphorylation of mTOR, JNK, and IRS1
Ser307 and by accumulation of multiple acylcarnitines in muscle, and it was reversed by the mTOR inhibitor, rapamycin. Our findings show that in the context of a dietary pattern that includes high fat consumption, BCAA contributes to development of obesity-associated insulin resistance.
The worldwide prevalences of diabetes mellitus (DM) and of heart failure (HF) have collectively been on the rise. HF accounts for a large portion of the cardiovascular mortality and morbidity ...associated with DM. DM increases the risk of developing heart failure by promoting atherosclerosis and exerting direct deleterious effects on the myocardium. Sodium-glucose co-transporter-2 (SGLT-2) inhibitors are agents approved for the treatment of DM; they exert their anti-hyperglycemic effects by blocking renal reabsorption of glucose and inducing glycosuria. SGLT-2 inhibitors have consistently decreased the hospitalization rate of HF and cardiovascular mortality in several clinical trials. SGLT-2 inhibitors also possess anti-inflammatory, anti-fibrotic, and antihypertensive in addition to beneficial effects on the myocardial metabolism, which may account for their heart failure benefits. However, further research still needs to be done to evaluate the use of SGLT-2 inhibitors in non-diabetic patients and their efficacy in preventing or treating different heart failure phenotypes.
•Heart failure accounts for a significant part of the diabetes-associated cardiovascular burden.•Diabetes mellitus increases the risk of heart failure by the development of atherosclerosis and diabetic cardiomyopathy.•Deposition of glycation end products, increased inflammation, and microvascular dysfunction contribute to the development of diabetic cardiomyopathy.•SGLT2 inhibitors decrease inflammation, increase ketogenesis and natriuresis, which could explain its utility in heart failure.•Further research is needed to define the role of SGLT2 inhibitors in the treatment of heart failure.
Purpose of Review
Heart failure is responsible for a significant part of diabetes-associated cardiovascular mortality and morbidity. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are novel ...agents approved for the treatment of diabetes mellitus; in recent clinical trials, these agents have shown a significant reduction in cardiovascular death and hospitalization secondary to heart failure.
Recent Findings
Clinical trials with specific heart failure outcomes have shown the benefit of SGLT-2 inhibitors in reducing the mortality and morbidity associated with heart failure. The guidelines for the management of diabetes mellitus recommend the preferential use of SGLT-2 inhibitors in patients with a history of cardiovascular disease.
Summary
SGLT-2 inhibitors are potential game changers in the treatment of heart failure. Guidelines for prescription of these agents help assess risk-benefit analysis and personalize treatment for maximal benefit.
Glycemic control is improved more after gastric bypass surgery (GBP) than after equivalent diet-induced weight loss in patients with morbid obesity and type 2 diabetes mellitus. We applied ...metabolomic profiling to understand the mechanisms of this better metabolic response after GBP. Circulating amino acids (AAs) and acylcarnitines (ACs) were measured in plasma from fasted subjects by targeted tandem mass spectrometry before and after a matched 10-kilogram weight loss induced by GBP or diet. Total AAs and branched-chain AAs (BCAAs) decreased after GBP, but not after dietary intervention. Metabolites derived from BCAA oxidation also decreased only after GBP. Principal components (PC) analysis identified two major PCs, one composed almost exclusively of ACs (PC1) and another with BCAAs and their metabolites as major contributors (PC2). PC1 and PC2 were inversely correlated with pro-insulin concentrations, the C-peptide response to oral glucose, and the insulin sensitivity index after weight loss, whereas PC2 was uniquely correlated with levels of insulin resistance (HOMA-IR). These data suggest that the enhanced decrease in circulating AAs after GBP occurs by mechanisms other than weight loss and may contribute to the better improvement in glucose homeostasis observed with the surgical intervention.
The transition from intravenous (IV) to subcutaneous (SQ) insulin in the hospitalized patient with diabetes or hyperglycemia is a key step in patient care. This review article suggests a stepwise ...approach to the transition in order to promote safety and euglycemia. Important components of the transition include evaluating the patient and clinical situation for appropriateness, recognizing factors that influence a safe transition, calculation of proper SQ insulin doses, and deciding the appropriate type of SQ insulin. This article addresses other clinical situations including the management of patients previously on insulin pumps and recommendations for patients requiring glucocorticoids and enteral tube feedings. The use of institutional and computerized protocols is discussed. Further research is needed regarding the transition management of subgroups of patients such as those with type 1 diabetes and end-stage renal disease.
Behavioral weight loss interventions achieve short-term success, but re-gain is common.
To compare 2 weight loss maintenance interventions with a self-directed control group.
Two-phase trial in which ...1032 overweight or obese adults (38% African American, 63% women) with hypertension, dyslipidemia, or both who had lost at least 4 kg during a 6-month weight loss program (phase 1) were randomized to a weight-loss maintenance intervention (phase 2). Enrollment at 4 academic centers occurred August 2003-July 2004 and randomization, February-December 2004. Data collection was completed in June 2007.
After the phase 1 weight-loss program, participants were randomized to one of the following groups for 30 months: monthly personal contact, unlimited access to an interactive technology-based intervention, or self-directed control. Main Outcome Changes in weight from randomization.
Mean entry weight was 96.7 kg. During the initial 6-month program, mean weight loss was 8.5 kg. After randomization, weight regain occurred. Participants in the personal-contact group regained less weight (4.0 kg) than those in the self-directed group (5.5 kg; mean difference at 30 months, -1.5 kg; 95% confidence interval CI, -2.4 to -0.6 kg; P = .001). At 30 months, weight regain did not differ between the interactive technology-based (5.2 kg) and self-directed groups (5.5 kg; mean difference -0.3 kg; 95% CI, -1.2 to 0.6 kg; P = .51); however, weight regain was lower in the interactive technology-based than in the self-directed group at 18 months (mean difference, -1.1 kg; 95% CI, -1.9 to -0.4 kg; P = .003) and at 24 months (mean difference, -0.9 kg; 95% CI, -1.7 to -0.02 kg; P = .04). At 30 months, the difference between the personal-contact and interactive technology-based group was -1.2 kg (95% CI -2.1 to -0.3; P = .008). Effects did not differ significantly by sex, race, age, and body mass index subgroups. Overall, 71% of study participants remained below entry weight.
The majority of individuals who successfully completed an initial behavioral weight loss program maintained a weight below their initial level. Monthly brief personal contact provided modest benefit in sustaining weight loss, whereas an interactive technology-based intervention provided early but transient benefit.
clinicaltrials.gov Identifier: NCT00054925.
Purpose of Review
Since the 2008 FDA guidance restructuring the design of trials for the approval of novel glucose-lowering agents, 13 medications have now been evaluated by dedicated cardiovascular ...outcome trials. All of the completed trials have included data (though with varying definitions) on rates of hospitalization for heart failure. This review is aimed at summarizing current heart failure outcome data available from cardiovascular safety trials for novel glucose-lowering agents in patients with type 2 diabetes mellitus.
Recent Findings
There appears to be growing evidence for the benefit of sodium–glucose cotransporter-2 inhibitors, and there are still not enough data to fully support the safety of glucagon-like peptide 1 receptor agonists in heart failure. Increased rates of hospitalization for heart failure were seen with both saxagliptin and alogliptin, and this has led to a class warning for all dipeptidyl peptidase-4 inhibitors.
Summary
Future studies should have a standardized definition of “hospitalization for heart failure,” should consider including hospitalization for heart failure as a component of the primary composite endpoint, and should provide a more detailed description of the baseline characteristics of enrolled study participants with heart failure.
Diabetes mellitus (DM) and chronic kidney disease (CKD) are intricately intertwined. DM is the most common cause of CKD. Adequate control of DM is necessary for prevention of progression of CKD, ...while careful management of the metabolic abnormalities in CKD will assist in achieving better control of DM. Two of the key organs involved in glucose production are the kidney and the liver. Furthermore, the kidney also plays a role in glucose filtration and reabsorption. In CKD, monitoring of glycemic control using traditional methods such as Hemoglobin A1c (Hba1c) must be done with caution secondary to associated hematological abnormalities in CKD. With regard to medication management in the care of patients with DM, CKD has significant effects. For example, the dosages of oral and non-insulin anti-hyperglycemic agents often need to be modified according to renal function. Insulin metabolism is altered in CKD, and a reduction in insulin dose is almost always needed. Dialysis also affects various aspects of glucose homeostasis, necessitating appropriate changes in therapy. Due to the aforementioned factors glycemic management in patients with DM and CKD can be quiet challenging.
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