Samy I. McFarlane

Osteoporosis and cardiovascular disease: brittle bones and boned arteries, is there a link?

Both osteoporosis and cardiovascular disease (CVD) are major public health problems leading to increased morbidity and mortality. Although traditionally viewed as separate disease entities that increase in prevalence with aging, accumulating evidence indicates that there are similar pathophysiological mechanisms underlying both diseases. In addition to menopause and advanced age, other risk factors for CVD such as dyslipidemia, oxidative stress, inflammation, hyperhomocystinemia, hypertension, and diabetes have also been associated with increased risk of low bone mineral density (LBMD). Elevated LDL and low HDL cholesterol are associated with LBMD, altered lipid metabolism is associated with both bone remodeling and the atherosclerotic process, which might explain, in part, the co-existence of osteoporosis and atherosclerosis in patients with dyslipidemia. Similarly, inflammation plays a pivotal role in both atherosclerosis and osteoporosis. Elevated plasma homocysteine levels are associated with both CVD and osteoporosis. Nitric oxide (NO), in addition to its known atheroprotective effects, appears to also play a role in osteoblast function and bone turnover. Supporting this notion, in a small randomized controlled trial, nitroglycerine (an NO donor) was found to be as effective as estrogen in preventing bone loss in women with surgical menopause. Statins, agents that reduce atherogenesis, also stimulate bone formation. Furthermore, bisphosphonates, used in the treatment of osteoporosis, have been shown to inhibit atherogenesis. Intravenous bisphosphonate therapy significantly decreases serum LDL and increases HDL in postmenopausal women.The exciting possibilities of newer pharmacological agents that effectively treat both osteoporosis and CVD hold considerable promise. However, it is important to emphasize that the current evidence linking both of these diseases is far from conclusive. Therefore, additional research is necessary to further characterize the relationship between these two common illnesses.

Dietary carbohydrate restriction as the first approach in diabetes management: Critical review and evidence base

The inability of current recommendations to control the epidemic of diabetes, the specific failure of the prevailing low-fat diets to improve obesity, cardiovascular risk, or general health and the persistent reports of some serious side effects of commonly prescribed diabetic medications, in combination with the continued success of low-carbohydrate diets in the treatment of diabetes and metabolic syndrome without significant side effects, point to the need for a reappraisal of dietary guidelines. The benefits of carbohydrate restriction in diabetes are immediate and well documented. Concerns about the efficacy and safety are long term and conjectural rather than data driven. Dietary carbohydrate restriction reliably reduces high blood glucose, does not require weight loss (although is still best for weight loss), and leads to the reduction or elimination of medication. It has never shown side effects comparable with those seen in many drugs. Here we present 12 points of evidence supporting the use of low-carbohydrate diets as the first approach to treating type 2 diabetes and as the most effective adjunct to pharmacology in type 1. They represent the best-documented, least controversial results. The insistence on long-term randomized controlled trials as the only kind of data that will be accepted is without precedent in science. The seriousness of diabetes requires that we evaluate all of the evidence that is available. The 12 points are sufficiently compelling that we feel that the burden of proof rests with those who are opposed.

Prevalence of CKD and Comorbid Illness in Elderly Patients in the United States: Results From the Kidney Early Evaluation Program (KEEP)

BACKGROUNDnElderly individuals with chronic kidney disease (CKD) have high rates of comorbid conditions, including cardiovascular disease and its risk factors, and CKD-related complications. In individuals aged > or = 65 years, we sought to describe the prevalence of CKD determined from laboratory test results in the Kidney Early Evaluation Program (KEEP; n = 27,017) and National Health and Nutrition Examination Survey (NHANES) 1999-2006 (n = 5,538) and the prevalence of diagnosed CKD determined from billing codes in the Medicare 5% sample (n = 1,236,946). In all 3 data sources, we also explored comorbid conditions and CKD-related complications.nnnMETHODSnCKD was identified as decreased estimated glomerular filtration rate (<60 mL/min/1.73 m(2)) or increased albumin-creatinine ratio in KEEP and NHANES; CKD was identified using International Classification of Diseases, Ninth Revision, Clinical Modification codes in Medicare. Investigated comorbid conditions included diabetes, hypertension, high cholesterol level, coronary artery disease, congestive heart failure, cerebrovascular disease, peripheral vascular disease, and cancer, and CKD-related complications included anemia, hypocalcemia, hyperphosphatemia, and hyperparathyroidism.nnnRESULTSnThe prevalence of CKD was approximately 44% in both KEEP and NHANES participants, and the prevalence of diagnosed CKD was 7% in Medicare beneficiaries. In all 3 data sets, the prevalence of CKD or diagnosed CKD was higher in participants aged > or = 80 years and those with comorbid conditions. For KEEP and NHANES participants, the prevalence of most comorbid conditions and CKD complications increased with decreasing estimated glomerular filtration rate. For participants with CKD stages 3-5, a total of 29.2% (95% CI, 27.8-30.6) in KEEP and 19.9% (95% CI, 17.0-23.1) in NHANES had anemia, 0.7% (95% CI, 0.4-0.9) and 0.6% (95% CI, 0.3-1.3) had hypocalcemia, 5.4% (95% CI, 4.7-6.1) and 6.4% (95% CI, 5.1-8.0) had hyperphosphatemia, and 52.0% (95% CI, 50.4-53.6) and 30.0% (95% CI, 25.9-34.3) had hyperparathyroidism, respectively.nnnCONCLUSIONSnCKD is common in the elderly population and is associated with high frequencies of concomitant comorbid conditions and biochemical abnormalities. Because CKD is not commonly diagnosed, greater emphasis on physician education may be beneficial.

Dietary carbohydrate restriction in type 2 diabetes mellitus and metabolic syndrome: time for a critical appraisal

Current nutritional approaches to metabolic syndrome and type 2 diabetes generally rely on reductions in dietary fat. The success of such approaches has been limited and therapy more generally relies on pharmacology. The argument is made that a re-evaluation of the role of carbohydrate restriction, the historical and intuitive approach to the problem, may provide an alternative and possibly superior dietary strategy. The rationale is that carbohydrate restriction improves glycemic control and reduces insulin fluctuations which are primary targets. Experiments are summarized showing that carbohydrate-restricted diets are at least as effective for weight loss as low-fat diets and that substitution of fat for carbohydrate is generally beneficial for risk of cardiovascular disease. These beneficial effects of carbohydrate restriction do not require weight loss. Finally, the point is reiterated that carbohydrate restriction improves all of the features of metabolic syndrome.

CKD in the United States: Kidney Early Evaluation Program (KEEP) and National Health and Nutrition Examination Survey (NHANES) 1999-2004

BACKGROUNDnThe prevalence of chronic kidney disease (CKD) is increasing in the United States, caused in part by older age and increasing prevalences of hypertension and type 2 diabetes. CKD is silent and undetected until advanced stages. The study of populations with earlier stages of kidney disease may improve outcomes of CKD.nnnMETHODSnThe Kidney Early Evaluation Program (KEEP), a National Kidney Foundation program, is a targeted community-based health-screening program enrolling individuals 18 years and older with diabetes, hypertension, or family history of kidney disease, diabetes, or hypertension. Participants who had received transplants or were on regular dialysis treatment were excluded from this analysis. The National Health and Nutrition Examination Survey (NHANES) 1999-2004 was a nationally representative cross-sectional survey; participants were interviewed in their homes and/or received standardized medical examinations in mobile examination centers.nnnRESULTSnOf the 61,675 KEEP participants, 16,689 (27.1%) were found to have CKD. In the NHANES sample of 14,632 participants, 2,734 (15.3%) had CKD. Older age, smoking, obesity, diabetes, hypertension, and cardiovascular disease were associated significantly with CKD in both KEEP and NHANES (P < 0.05 for all). Of note, the likelihood for CKD in African Americans differed between KEEP (odds ratio, 0.81; P < 0.001) and NHANES (odds ratio, 1.10; P = 0.2).nnnCONCLUSIONnA greater prevalence of CKD was detected in the KEEP screening than in the NHANES data. KEEP has the limitations common to population-screening studies and conclusions for population-attributable risk may be limited. The targeted nature of the KEEP screening program and the large sample size with clinical characteristics comparable to NHANES validates KEEP as a valuable cohort to explore health associations for the CKD and at-risk-for-CKD populations in the United States.

CKD and cardiovascular disease in screened high-risk volunteer and general populations: the Kidney Early Evaluation Program (KEEP) and National Health and Nutrition Examination Survey (NHANES) 1999-2004.

BACKGROUNDnChronic kidney disease (CKD) is recognized as an independent cardiovascular disease risk state. The relationship between CKD and cardiovascular disease in volunteer and general populations has not been explored.nnnMETHODSnThe National Kidney Foundation Kidney Early Evaluation Program (KEEP) is a community-based health-screening program to raise kidney disease awareness and detect CKD for early disease intervention in individuals 18 years or older with diabetes, hypertension, or family history of kidney disease, diabetes, or hypertension. KEEP volunteers completed surveys and underwent blood pressure and laboratory testing. Estimated glomerular filtration rate (eGFR) was computed, and urine albumin-creatinine ratio (ACR) was measured. In KEEP, CKD was defined as eGFR less than 60 mL/min/1.73 m(2) or ACR of 30 mg/g or greater. Cardiovascular disease was defined as self-reported myocardial infarction or stroke. Data were compared with National Health and Nutrition Examination Survey (NHANES) 1999-2004 data for prevalence of cardiovascular disease risk factors and cardiovascular outcomes.nnnRESULTSnOf 69,244 KEEP participants, mean age was 53.4 +/- 15.7 years, 68.3% were women, 33.0% were African American, and 27.6% had diabetes. Of 17,061 NHANES participants, mean age was 45.1 +/- 0.27 years, 52% were women, 11.2% were African American, and 6.7% had diabetes. In KEEP, 26.8% had CKD, and in NHANES, 15.3%. ACR was the dominant positive screening test for younger age groups, and eGFR, for older age groups, for both populations. Prevalences of myocardial infarction or stroke were 16.5% in KEEP and 15.1% in NHANES (P < 0.001) and 7.8% in KEEP and 3.7% in NHANES (P < 0.001) for individuals with and without CKD, respectively. In adjusted analysis of both KEEP and NHANES data, CKD was associated with a significantly increased risk of prevalent myocardial infarction or stroke (odds ratio, 1.34; 95% confidence interval, 1.25 to 1.43; odds ratio, 1.37; 95% confidence interval, 1.10 to 1.70, respectively). In KEEP, short-term mortality was greater in individuals with CKD (1.52 versus 0.33 events/1,000 patient-years).nnnCONCLUSIONSnCKD is independently associated with myocardial infarction or stroke in participants in a voluntary screening program and a randomly selected survey population. Heightened concerns regarding risks in volunteers yielded greater cardiovascular disease prevalence in KEEP, which was associated with increased short-term mortality.

Antiepileptic drugs and bone metabolism

Anti-epileptic medications encompass a wide range of drugs including anticonvulsants, benzodiazepines, enzyme inducers or inhibitors, with a variety effects, including induction of cytochrome P450 and other enzyme, which may lead to catabolism of vitamin D and hypocalcemia and other effects that may significantly effect the risk for low bone mass and fractures. With the current estimates of 50 million people worldwide with epilepsy together with the rapid increase in utilization of these medications for other indications, bone disease associated with the use of anti-epileptic medications is emerging as a serious health threat for millions of people. Nevertheless, it usually goes unrecognized and untreated. In this review we discuss the pathophysiologic mechanisms of bone disease associated with anti-epileptic use, including effect of anti-epileptic agents on bone turnover and fracture risk, highlighting various strategies for prevention of bone loss and associated fractures a rapidly increasing vulnerable population.

The case for low carbohydrate diets in diabetes management

A low fat, high carbohydrate diet in combination with regular exercise is the traditional recommendation for treating diabetes. Compliance with these lifestyle modifications is less than satisfactory, however, and a high carbohydrate diet raises postprandial plasma glucose and insulin secretion, thereby increasing risk of CVD, hypertension, dyslipidemia, obesity and diabetes. Moreover, the current epidemic of diabetes and obesity has been, over the past three decades, accompanied by a significant decrease in fat consumption and an increase in carbohydrate consumption. This apparent failure of the traditional diet, from a public health point of view, indicates that alternative dietary approaches are needed. Because carbohydrate is the major secretagogue of insulin, some form of carbohydrate restriction is a prima facie candidate for dietary control of diabetes. Evidence from various randomized controlled trials in recent years has convinced us that such diets are safe and effective, at least in short-term. These data show low carbohydrate diets to be comparable or better than traditional low fat high carbohydrate diets for weight reduction, improvement in the dyslipidemia of diabetes and metabolic syndrome as well as control of blood pressure, postprandial glycemia and insulin secretion. Furthermore, the ability of low carbohydrate diets to reduce triglycerides and to increase HDL is of particular importance. Resistance to such strategies has been due, in part, to equating it with the popular Atkins diet. However, there are many variations and room for individual physician planning. Some form of low carbohydrate diet, in combination with exercise, is a viable option for patients with diabetes. However, the extreme reduction of carbohydrate of popular diets (<30 g/day) cannot be recommended for a diabetic population at this time without further study. On the other hand, the dire objections continually raised in the literature appear to have very little scientific basis. Whereas it is traditional to say that more work needs to be done, the same is true of the assumed standard low fat diets which have an ambiguous record at best. We see current trends in the national dietary recommendations as a positive sign and an appropriate move in the right direction.

Diabetes mellitus and CKD awareness: the Kidney Early Evaluation Program (KEEP) and National Health and Nutrition Examination Survey (NHANES).

BACKGROUNDnDiabetes contributes to increased morbidity and mortality in patients with chronic kidney disease (CKD). We sought to describe CKD awareness and identify factors associated with optimal glycemic control in diabetic and nondiabetic individuals both aware and unaware of CKD.nnnMETHODSnThis cross-sectional analysis compared Kidney Early Evaluation Program (KEEP) and National Health and Nutrition and Examination Survey (NHANES) 1999 to 2006 participants with diabetes and CKD. CKD was defined and staged using glomerular filtration rate (estimated by using the 4-variable Modification of Diet in Renal Disease Study equation) and urine albumin-creatinine ratio. NHANES defined diabetes as self-reported diabetes or fasting plasma blood glucose level of 126 mg/dL or greater, and KEEP as self-reported diabetes or diabetic retinopathy, use of diabetes medications, fasting blood glucose level of 126 mg/dL or greater, or nonfasting glucose level of 200 mg/dL or greater.nnnRESULTSnOf 77,077 KEEP participants, 20,200 (26.2%) were identified with CKD and 23,082 (29.9%) were identified with diabetes. Of 9,536 NHANES participants, 1,743 (18.3%) were identified with CKD and 1,127 (11.8%) were identified with diabetes. Of KEEP participants with diabetes and CKD (n = 7,853), 736 (9.4%) were aware of CKD. Trends in lack of CKD awareness were similar for KEEP participants with and without diabetes. Unaware participants with and without diabetes identified with stages 1 and 2 CKD were less likely to reach target glucose levels, defined as fasting glucose level less than 126 mg/dL or nonfasting glucose level less than 140 mg/dL, than those with stages 3 to 5 (odds ratio, 0.69; 95% confidence interval, 0.62 to 0.78; odds ratio, 0.69; 95% confidence interval, 0.58 to 0.81; P < 0.001, respectively).nnnCONCLUSIONnOur data support that KEEP, as a targeted screening program, is a more enriched population with CKD and comorbid diabetes than NHANES. In addition, our findings highlight the relationship between dysglycemia and early stages of unidentified CKD.

Race/Ethnicity, Sleep Duration, and Diabetes Mellitus: Analysis of the National Health Interview Survey

BACKGROUNDnThe effect of race/ethnicity on the risk of diabetes associated with sleep duration has not been systematically investigated. This study assessed whether blacks reporting short (<6 hours) or long (>8 hours) sleep durations were at greater risk for diabetes than their white counterparts. In addition, this study also examined whether the influence of race/ethnicity on associations between abnormal sleep durations and the presence of diabetes were independent of individuals sociodemographic and medical characteristics.nnnMETHODSnA total of 29,818 Americans (age range: 18-85 years) enrolled in the 2005 National Health Interview Survey, a cross-sectional household interview survey, provided complete data for this analysis.nnnRESULTSnOf the sample, 85% self-ascribed their ethnicity as white and 15% as black. The average age was 47.4 years, and 56% were female. Results of univariate regression analysis adjusting for medical comorbidities showed that black and white participants who reported short sleep duration (<6 hours) were more likely to have diabetes than individuals who reported sleeping 6 to 8 hours (odds ratios 1.66 and 1.87, respectively). Likewise, black and white participants reporting long sleep duration (>8 hours) had a greater likelihood of reporting diabetes compared with those sleeping 6 to 8 hours (odds ratios 1.68 and 2.33, respectively). Significant interactions of short and long sleep with black and white race were observed. Compared with white participants, greater diabetes risk was associated with being short or long sleepers of black race.nnnCONCLUSIONnThe present findings suggest that American short and long sleepers of black race may be at greater risk for diabetes independently of their sociodemographic profile or the presence of comorbid medical conditions, which have been shown to influence habitual sleep durations. Among black individuals at risk for diabetes, healthcare providers should stress the need for adequate sleep.