Stuart R. Chipkin

Tight Glycemic Control in Diabetic Coronary Artery Bypass Graft Patients Improves Perioperative Outcomes and Decreases Recurrent Ischemic Events

Background—This study sought to determine whether tight glycemic control with a modified glucose-insulin-potassium (GIK) solution in diabetic coronary artery bypass graft (CABG) patients would improve perioperative outcomes. Methods and Results—One hundred forty-one diabetic patients undergoing CABG were prospectively randomized to tight glycemic control (serum glucose, 125 to 200 mg/dL) with GIK or standard therapy (serum glucose <250 mg/dL) using intermittent subcutaneous insulin beginning before anesthesia and continuing for 12 hours after surgery. GIK patients had lower serum glucose levels (138±4 versus 260±6 mg/dL; P <0.0001), a lower incidence of atrial fibrillation (16.6% versus 42%; P =0.0017), and a shorter postoperative length of stay (6.5±0.1 versus 9.2±0.3 days; P =0.003). GIK patients also showed a survival advantage over the initial 2 years after surgery (P =0.04) and decreased episodes of recurrent ischemia (5% versus 19%; P =0.01) and developed fewer recurrent wound infections (1% versus 10%, P =0.03). Conclusions—Tight glycemic control with GIK in diabetic CABG patients improves perioperative outcomes, enhances survival, and decreases the incidence of ischemic events and wound complications.

The Society of Thoracic Surgeons Practice Guideline Series: Blood Glucose Management During Adult Cardiac Surgery

The Society of Thoracic Surgeons Practice Guideline Series : Blood Glucose Management During Adult Cardiac Surgery

Effect of Statins on Skeletal Muscle Function

Background— Many clinicians believe that statins cause muscle pain, but this has not been observed in clinical trials, and the effect of statins on muscle performance has not been carefully studied. Methods and Results— The Effect of Statins on Skeletal Muscle Function and Performance (STOMP) study assessed symptoms and measured creatine kinase, exercise capacity, and muscle strength before and after atorvastatin 80 mg or placebo was administered for 6 months to 420 healthy, statin-naive subjects. No individual creatine kinase value exceeded 10 times normal, but average creatine kinase increased 20.8±141.1 U/L (P<0.0001) with atorvastatin. There were no significant changes in several measures of muscle strength or exercise capacity with atorvastatin, but more atorvastatin than placebo subjects developed myalgia (19 versus 10; P=0.05). Myalgic subjects on atorvastatin or placebo had decreased muscle strength in 5 of 14 and 4 of 14 variables, respectively (P=0.69). Conclusions— These results indicate that high-dose atorvastatin for 6 months does not decrease average muscle strength or exercise performance in healthy, previously untreated subjects. Nevertheless, this blinded, controlled trial confirms the undocumented impression that statins increase muscle complaints. Atorvastatin also increased average creatine kinase, suggesting that statins produce mild muscle injury even among asymptomatic subjects. This increase in creatine kinase should prompt studies examining the effects of more prolonged, high-dose statin treatment on muscular performance. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00609063.

Glucose-insulin-potassium solutions improve outcomes in diabetics who have coronary artery operations

BACKGROUND This study was undertaken to determine whether glucose-insulin-potassium (GIK) would improve myocardial performance and limit morbidity after coronary artery bypass grafting in diabetic patients. METHODS Forty consecutive coronary artery bypass grafting patients with medically treated diabetes mellitus were prospectively randomly assigned to either a GIK group (n = 20; 500 mL D5W + 80 U regular insulin + 40 mEq KCl 30 mL/hour) or a no-GIK group (n = 20; D5W at 30 mL/hour). The GIK was begun at anesthetic induction and continued for 12 hours postoperatively. RESULTS Patients treated with GIK had higher postoperative cardiac indices (2.88 +/- 0.50 versus 2.20 +/- 0.39 L/minute per square meter; p < 0.0001), lower inotrope scores (0.40 +/- 0.68 versus 1.25 +/- 1.44; p = 0.05), less weight gain (5.80 +/- 3.76 versus 13.85 +/- 6.52 pounds; p < 0.0001), and had shorter times of ventilator support (8.35 +/- 2.60 versus 13.45 +/- 7.33 hours; p = 0.0128). They had a significantly lower prevalence of atrial fibrillation (15% versus 60%; p = 0.003), and shorter hospital stays (6.70 +/- 1.52 versus 10.15 +/- 6.62 days; p = 0.02). CONCLUSIONS Substrate enhancement with GIK in diabetic patients improved myocardial performance and resulted in faster recovery after coronary artery bypass grafting.

Exercise and diabetes.

As rates of diabetes mellitus and obesity continue to increase, physical activity continues to be a fundamental form of therapy. Exercise influences several aspects of diabetes, including blood glucose concentrations, insulin action and cardiovascular risk factors. Blood glucose concentrations reflect the balance between skeletal muscle uptake and ambient concentrations of both insulin and counterinsulin hormones. Difficulties in predicting the relative impact of these factors can result in either hypoglycemia or hyperglycemia. Despite the variable impact of exercise on blood glucose, exercise consistently improves insulin action and several cardiovascular risk factors. Beyond the acute impact of physical activity, long-term exercise behaviors have been repeatedly associated with decreased rates of type 2 diabetes. While exercise produces many benefits, it is not without risks for patients with diabetes mellitus. In addition to hyperglycemia, from increased hepatic glucose production, insufficient insulin levels can foster ketogenesis from excess concentrations of fatty acids. At the opposite end of the glucose spectrum, hypoglycemia can result from excess glucose uptake due to either increased insulin concentrations, enhanced insulin action or impaired carbohydrate absorption. To decrease the risk for hypoglycemia, insulin doses should be reduced prior to exercise, although some insulin is typically still needed. Although precise risks of exercise on existing diabetic complications have not been well studied, it seems prudent to consider the potential to worsen nephropathy or retinopathy, or to precipitate musculoskeletal injuries. There is more substantive evidence that autonomic neuropathy may predispose patients to arrhythmias. Of clear concern, increased physical activity can precipitate a cardiac event in those with underlying CAD. Recognizing these risks can prompt actions to minimize their impact. Positive actions that are part of exercise programs for diabetic patients emphasize SMBG, foot care and cardiovascular functional assessment. SMBG provides critical information on the impact of exercise and is recommended for all patients before, during and after exercise. More frequent monitoring (and for longer periods following exercise) is recommended for those with hypoglycemia unawareness or those performing high-intensity exercise. Preventing the sequelae of an exercise-induced severe hypoglycemic reaction can be as simple as carrying glucose tablets or gel, a diabetic identification bracelet or card, or exercising with an individual who is aware of the circumstances. In addition to blood glucose concentrations, proper foot care is critical to people with diabetes who exercise and includes considering type of shoe, type of exercise, inspection of skin surfaces and appropriate evaluation and treatment of lesions (calluses and others). Those with severe neuropathy can consider alternatives to weight-bearing exercises. Precipitation of clinical CAD is of great concern for all diabetic patients participating in exercise activities. Although a sufficiently sensitive and specific screening test for coronary disease has not been identified, those planning an exercise program of moderate intensity or greater should be evaluated. Initial cardiac assessment should include exercise testing as well as identifying risk for autonomic neuropathy. In addition to noting maximal heart rate and blood pressure as well as ischemic changes, exercise tolerance testing can identify anginal thresholds and patients with asymptomatic ischemia. Those without symptoms should be counseled regarding target pulse rates to avoid inducing ischemia. Ischemic changes need to be evaluated for either further diagnostic testing or pharmacological intervention. For patients with diabetes mellitus, the overall benefits of exercise are clearly significant. Clinicians and patients must work together to maximize these benefits while minimizing risks for negative consequences. Identifying and preventing potential problems beforehand can reduce adverse outcomes and promote this important approach to healthy living.

Effects of exercise on energy-regulating hormones and appetite in men and women.

When previously sedentary men and women follow exercise training programs with ad libitum feeding, men lose body fat, but women do not. The purpose of this study was to evaluate whether this observation could be related to sex differences in the way energy-regulating hormones and appetite perception respond to exercise. Eighteen (9 men, 9 women) overweight/obese individuals completed four bouts of exercise with energy added to the baseline diet to maintain energy balance (BAL), and four bouts without energy added to induce energy deficit (DEF). Concentrations of acylated ghrelin, insulin, and leptin, as well as appetite ratings were measured in response to a meal after a no-exercise baseline and both exercise conditions. In men, acylated ghrelin area under the curve (AUC) was not different between conditions. In women, acylated ghrelin AUC was higher after DEF (+32%) and BAL (+25%), and the change from baseline was higher than men (P < 0.05). In men, insulin AUC was reduced (-17%) after DEF (P < 0.05), but not BAL. In women, insulin AUC was lower (P < 0.05) after DEF (-28%) and BAL (-15%). Leptin concentrations were not different across conditions in either sex. In men, but not in women, appetite was inhibited after BAL relative to DEF. The results indicate that, in women, exercise altered energy-regulating hormones in a direction expected to stimulate energy intake, regardless of energy status. In men, the response to exercise was abolished when energy balance was maintained. The data are consistent with the paradigm that mechanisms to maintain body fat are more effective in women.

Independent and combined effects of exercise training and metformin on insulin sensitivity in individuals with prediabetes.

OBJECTIVE Physical activity or metformin enhances insulin sensitivity and opposes the progression from prediabetes to type 2 diabetes. The combination may be more effective because each treatment stimulates AMP-activated protein kinase activity in skeletal muscle. We evaluated the effects of exercise training plus metformin on insulin sensitivity in men and women with prediabetes, compared with each treatment alone. RESEARCH DESIGN AND METHODS For 12 weeks, men and women with prediabetes were assigned to the following groups: placebo (P), 2,000 mg/day metformin (M), exercise training with placebo (EP), or exercise training with metformin (EM) (n = 8 per group). Before and after the intervention, insulin sensitivity was measured by euglycemic hyperinsulinemic (80 mU/m2/min) clamp enriched with [6,6-2H]glucose. Changes due to intervention were compared across groups by repeated-measures ANOVA. RESULTS All three interventions increased insulin sensitivity (P < 0.05) relative to the control group. The mean rise was 25–30% higher after EP than after either EM or M, but this difference was not significant. CONCLUSIONS Insulin sensitivity was considerably higher after 12 weeks of exercise training and/or metformin in men and women with prediabetes. Subtle differences among condition means suggest that adding metformin blunted the full effect of exercise training.

Effects of aggressive versus moderate glycemic control on clinical outcomes in diabetic coronary artery bypass graft patients.

Objective:This study sought to determine whether aggressive glycemic control (90–120 mg/dL) would result in more optimal clinical outcomes and less morbidity than moderate glycemic control (120–180 mg/dL) in diabetic patients undergoing coronary artery bypass graft (CABG) surgery. Summary of Background Data:Maintaining serum glucose levels between 120 and 180 mg/dL with continuous insulin infusions decreases morbidity in diabetic patients undergoing CABG surgery. Studies in surgical patients requiring prolonged ventilation suggest that aggressive glycemic control (<120 mg/dL) may improve survival; however, its effect in diabetic CABG patients is unknown. Methods:Eighty-two diabetic patients undergoing CABG were prospectively randomized to aggressive glycemic control (90–120 mg/dL) or moderate glycemic control (120–180 mg/dL) using continuous intravenous insulin solutions (100 units regular insulin in 100 mL: normal saline) beginning at the induction of anesthesia and continuing for 18 hours after CABG. Primary end points were the incidence of major adverse events (major adverse events = 30-day mortality, myocardial infarction, neurologic events, deep sternal infections, and atrial fibrillation), the level of serum glucose, and the incidence of hypoglycemic events. Results:There were no differences in the incidence of major adverse events between the groups (17 moderate vs 15 aggressive; P = 0.91). Patients with aggressive control had a lower mean glucose at the end of 18 hours of insulin infusion (135 ± 12 mg/dL moderate vs 103 ± 17 mg/dL aggressive; P < 0.0001). Patients with aggressive control had a higher incidence of hypoglycemic events (4 vs 30; P < 0.0001). Conclusions:In diabetic patients undergoing CABG surgery, aggressive glycemic control increases the incidence of hypoglycemic events and does not result in any significant improvement in clinical outcomes that can be achieved with moderate control. Clinical Trials.gov (ID #NCT00460499)

Continuous glucose monitoring counseling improves physical activity behaviors of individuals with type 2 diabetes: A randomized clinical trial

AIMS Despite the known benefits, 60% of individuals with diabetes do not engage in regular physical activity (PA). This pilot study tested the effects of a counseling intervention using continuous glucose monitoring system (CGMS) feedback on PA self-efficacy, PA levels, and physiological variables. METHODS Adults (N=52) with type 2 diabetes (non-insulin requiring, inactive) were randomized to intervention (n=27) or control (n=25) groups. Both groups received 90min of diabetes education with a follow-up phone call 4 weeks later. The intervention group also received counseling derived from self-efficacy theory. This intervention included feedback on each participants CGMS graph and used role model CGMS graphs to clearly depict glucose reductions in response to PA. Outcomes were assessed at baseline and 8 weeks. RESULTS Participants receiving the intervention had higher self-efficacy scores than the control group for sticking to activity/resisting relapse at 8 weeks (p<0.05), indicating more confidence in maintaining a PA program. Intervention group participants light/sedentary activity minutes decreased significantly (p<0.05), moderate activity minutes increased significantly (p<0.05), and, HbA1c and BMI decreased significantly (p<0.05). CONCLUSIONS These data suggest that PA counseling interventions using CGMS feedback for individuals with type 2 diabetes may improve PA levels and reduce risk factors for diabetes-related complications.

Use of Focus Groups to Explore Nutrition Practices and Health Beliefs of Urban Caribbean Latinos With Diabetes

OBJECTIVE Although Caribbean Latinos are two to three times more likely than non-Hispanic whites to develop diabetes, cultural influences on nutrition and health are poorly understood. To provide insight into important features of diabetes prevention and management, we conducted focus groups to explore nutrition practices and health beliefs. RESEARCH DESIGN AND METHODS Thirty low-income urban Caribbean Latinos with non-insulin-dependent diabetes mellitus (NIDDM) and four familymembers participated in four focus group interviews that were conducted in Boston and Cambridge, Massachusetts. Interviews were conducted in Spanish, were tape recorded, and were led and analyzed by Latino professionals from a community-based health organization. RESULTS Consistent themes described by participants were feelings of social isolation, little understanding of long-term consequences of diabetes, fatalism regarding the course of the disease, multiple barriers todiet and exercise interventions, skepticism regarding the value of preventive health behaviors, prevalent use of traditional nonmedicai remedies, and a clear need for culturally sensitive health-care providers and services. CONCLUSIONS The information from focus groups provides useful information for planning innovative intervention programs for chronic disease risk reduction that emphasize practical skills development, family/peer networks, empowerment techniques, and bilingual providers. We conclude that the focus group technique can be used effectively with low-income, urban minority populations to provide information on lifestyle behaviors and beliefs regarding chronic diseases that impact on health and nutritional status.