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

With its discovery in 1920, the molecule vitamin D achieved prominence as a nutritionally essential vitamin important for calcium homeostasis, particularly in the intestine and bone. Then in 1932, the elucidation of vitamin D's chemical structure revealed that this vitamin was in fact a steroid. But it was not until the late 1960s that it was appreciated that the steroid vitamin D was a precursor of a new steroid hormone, 1alpha,25(OH)2-vitamin D3 [1alpha,25(OH)2D3], that is produced by the kidney acting as an endocrine gland. The discovery in 1969 of the nuclear vitamin D receptor (VDR) for 1alpha,25(OH)2D3 initiated a two-decade-long proliferation of reports that collectively described the broad sphere of influence of the vitamin D endocrine system that is defined by the presence of the VDR in over 30 tissue/organs of man. The new genomic frontiers defined by the cellular presence of the VDR include the immune system's B and T lymphocytes, hair follicle, muscle, adipose tissue, bone marrow, and cancer cells. Unexpectedly in the mid 1980s, a new world of 1alpha,25(OH)2D3-mediated rapid responses (RR) was discovered. These were responses that occurred too rapidly (minutes to an hour) to be explained as the simple consequence of the nuclear VDR regulating gene transcription. Some RR examples include the rapid intestinal absorption of calcium (transcaltachia), secretion of insulin by pancreatic beta-cells, opening of voltage-gated Ca2+ and Cl- channels in osteoblasts, and the rapid migration of endothelial cells. The question then arose as to whether there was a second receptor, apart from the nuclear VDR, which responded to the presence of 1alpha,25(OH)2D3 to generate RR? After some false starts, it now appears that the classic VDR, long known to reside in the cell nucleus, in some cells is also associated with caveolae present in the plasma membrane. Furthermore, the chemical properties of the conformationally flexible 1alpha,25(OH)2D3 allow it to generate different shaped ligands for the VDR that are selective either for genomic or for RR. This minireview summarizes a proposed conformational ensemble model of the VDR that provides insight into how different ligand shapes of 1alpha,25(OH)2D3 acting through the VDR in different cellular locations can selectively mediate both genomic and RR.

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Minireview: vitamin D receptor: new assignments for an already busy receptor. - eScholarship

To achieve good metabolic control in diabetes and keep long term, a combination of changes in lifestyle and pharmacological treatment is necessary. Achieving near-normal glycated hemoglobin significantly, decreases risk of macrovascular and microvascular complications. At present there are different treatments, both oral and injectable, available for the treatment of type 2 diabetes mellitus (T2DM). Treatment algorithms designed to reduce the development or progression of the complications of diabetes emphasizes the need for good glycaemic control. The aim of this review is to perform an update on the benefits and limitations of different drugs, both current and future, for the treatment of T2DM. Initial intervention should focus on lifestyle changes. Moreover, changes in lifestyle have proven to be beneficial, but for many patients is a complication keep long term. Physicians should be familiar with the different types of existing drugs for the treatment of diabetes and select the most effective, safe and better tolerated by patients. Metformin remains the first choice of treatment for most patients. Other alternative or second-line treatment options should be individualized depending on the characteristics of each patient. This article reviews the treatments available for patients with T2DM, with an emphasis on agents introduced within the last decade.

Update on the treatment of type 2 diabetes mellitus

Renin-angiotensin-aldosterone (RAAS): The ubiquitous system for homeostasis and pathologies.

Context: Observational studies report consistent associations between low vitamin D concentration and increased glycemia and risk of type 2 diabetes, but results of randomized controlled trials (RCTs) are mixed. Objective: The objective of the study was to systematically review RCTs that report on the effects of vitamin D supplementation on glucose homeostasis or diabetes prevention. Data Sources: Sources of data for the study were MEDLINE, EMBASE, SCOPUS, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Health Technology Assessment, and Science Citation Index from inception to June 2013. Study Selection: Study selection was trials that compared vitamin D3 supplementation with placebo or a non-vitamin D supplement in adults with normal glucose tolerance, prediabetes, or type 2 diabetes. Data Extraction and Synthesis: Two reviewers collected data and assessed trial quality using the Cochrane Risk of Bias tool. Random-effects models were used to estimate mean differences...

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Clinical review: Effect of vitamin D3 supplementation on improving glucose homeostasis and preventing diabetes: a systematic review and meta-analysis.

Background: Elevated renin-angiotensin-aldosterone system (RAAS) activity is an important mechanism in the development of hypertension. Both obesity and 25-hydroxy vitamin D [25(OH)D] deficiency have been associated with hypertension and augmented renin-angiotensin system (RAS) activity. We tried to test the hypothesis that vitamin D deficiency and obesity are associated with increased RAS activity in Indian patients with hypertension. Materials and Methods: Fifty newly detected hypertensive patients were screened. Patients with secondary hypertension, chronic kidney disease, or coronary artery disease were excluded. Patients underwent measurement of vitamin D and plasma renin and plasma aldosterone concentrations. They were divided into three groups according to their baseline body mass index (BMI; normal <25 kg/m 2 , overweight 25-29.9 kg/m 2 and obese ≥30 kg/m 2 ) and 25(OH)D levels (deficient <20 ng/ml, insufficient 20-29 ng/ml and optimal ≥30 ng/ml). Results: A total of 50 (male:female = 32:18) patients were included, with a mean age of 49.5 ± 7.8 years, mean BMI of 28.3 ± 3.4 kg/m 2 and a mean 25(OH)D concentration of 18.5 ± 6.4 ng/ml. Mean systolic blood pressure (SBP) was 162.4 ± 20.2 mm Hg and mean diastolic blood pressure (DBP) was 100.2 ± 11.2 mm Hg. All the three blood pressure parameters [SBP, DBP and mean arterial pressure (MAP)] were significantly higher among individuals with lower 25(OH)D levels. The P values for trends in SBP, DBP and MAP were 0.009, 0.01 and 0.007, respectively. Though all the three blood pressure parameters (SBP, DBP and MAP) were higher among individuals with higher BMIs, they were not achieving statistical significance. Increasing trends in PRA and PAC were noticed with lower 25(OH)D and higher BMI levels. Conclusion: Vitamin D deficiency and obesity are associated with stimulation of RAAS activity. Vitamin D supplementation along with weight loss may be studied as a therapeutic strategy to reduce tissue RAS activity in individualswith Vitamin D deficiency and obesity.

Renin–angiotensin system activity in vitamin D deficient, obese individuals with hypertension: An urban Indian study

Background: Bone mineral density (BMD) is known to be affected by serum 25-hydroxyvitamin D (25(OH) D) levels, intact parathyroid hormone (iPTH) levels. Indian data pertinent to above observation is scant. Our study aimed to investigate the relationships between serum 25-hydroxyvitamin D (25(OH) D) levels, intact parathyroid hormone (iPTH) levels and bone mineral density (BMD) in a cohort of Indian patients. Materials and Methods: Adults with or without fragility fractures with low BMD at the hip or lumbar spine were evaluated clinically along with laboratory investigations. T-scores of the hip and spine were derived from BMD-DEXA (dual-energy X-ray absorptiometry). Multivariate regression models were used to investigate the relationships between serum 25(OH) D, iPTH and BMD. Results: Total of 102 patients (male:female = 38:64) with a mean age of 62.5 ± 6.4 years were included in the study. Forty-four patients had osteopenia. Osteoporosis was present in 58 patients. The mean values for serum 25(OH) D and iPTH levels were 21.3 ± 0.5 ng/ml and 53.1 ± 22.3 pg/ml, respectively. In 84.3% of patients, serum 25(OH) D levels were below 30 ng/ml (Normal = 30–74 ng/ml), confirming vitamin D deficiency. There was no association between 25(OH) D levels and BMD at the hip or lumbar spine (P = 0.473 and 0.353, respectively). Both at the hip and lumbar spine; iPTH levels, male gender, body mass index (BMI) and age were found to be significant predictors of BMD. Patients with higher BMI had significantly lower BMD and T-score. At levels <30 ng/ml, 25(OH) D was negatively associated with iPTH (P = 0.041). Conclusion: Among our cohort of patients with low BMD, no direct relationship between serum 25(OH) D levels and BMD was observed. However, a negative correlation between iPTH and 25(OH) D at serum 25(OH) D concentrations <30 ng/ml. Serum iPTH levels showed a significant negative association with BMD at the hip and lumbar spine. Our findings underscore the critical role of parathyroid hormone in bone metabolism and health.

Correlation of vitamin D, bone mineral density and parathyroid hormone levels in adults with low bone density.

Acute pancreatitis is a medical emergency. Alcohol and gallstones are the most common etiologies accounting for 60%-75% cases. Other important causes include postendoscopic retrograde cholangiopancreatography procedure, abdominal trauma, drug toxicity, various infections, autoimmune, ischemia, and hereditary causes. In about 15% of cases the cause remains unknown (idiopathic pancreatitis). Metabolic conditions giving rise to pancreatitis are less common, accounting for 5%-10% cases. The causes include hypertriglyceridemia, hypercalcemia, diabetes mellitus, porphyria, and Wilson's disease. The episodes of pancreatitis tend to be more severe. In cases of metabolic pancreatitis, over and above the standard routine management of pancreatitis, careful management of the underlying metabolic abnormalities is of paramount importance. If not treated properly, it leads to recurrent life-threatening bouts of acute pancreatitis. We hereby review the pathogenesis and management of various causes of metabolic pancreatitis.

Metabolic pancreatitis: Etiopathogenesis and management.

Aim Diabetes and vitamin D deficiency are widely prevalent in India. Studies have proven correlation between low vitamin D levels and pulmonary tuberculosis (PTB) and low vitamin D levels and insulin resistance. We evaluated the effects of vitamin D supplementation on type 2 diabetes mellitus patients with pulmonary tuberculosis (PTB). Methods Forty-five subjects (M:F = 34:11) were screened. Inclusion criteria were age >15 years, newly diagnosed PTB cases with uncontrolled diabetes, serum vitamin D  Results Fifteen patients having vitamin D > 20 ng/ml were excluded. Age of the patients was 42.9 ± 13.2 years and serum vitamin D levels were 18.4 ± 15.3 ng/ml. Sputum smear conversion was 6 weeks in group 1 versus 8 weeks in group 2 ( p  = 0.067). Glycated hemoglobin levels reduced from 11.1 ± 1.3 to 7.7 ± 0.9 in group1 versus 10.3 ± 1.2 to 7.8 ± 1.1 ( p  > 0.1). Conclusion Vitamin D can serve as adjuvant treatment of tuberculosis in diabetics with vitamin D deficiency. Further studies are required to validate this observation and define a cut off for vitamin D level to prevent immunological alterations.

Effect of vitamin D supplementation in type 2 diabetes patients with pulmonary tuberculosis

Background: Diabetes mellitus is associated with high cardiovascular risk. Carotid intima media thickness (CIMT) is used commonly as a noninvasive test for the assessment of degree of atherosclerosis. The objective of this study was to find out the cut-off point for CIMT for ischemic stroke in patients with type 2 diabetes mellitus (T2DM) and to correlate CIMT with various parameters like smoking, hypertension, lipid profile and duration of T2DM. Materials and Methods: A total of 80 subjects in the age group of 30-75 years (M:F = 57:23) were selected and divided into three groups, i.e. diabetes with ischemic stroke, diabetes and healthy subjects. All the participants were subjected to B-mode ultrasonography of both common carotid arteries to determine CIMT, along with history taking, physical examination and routine laboratory investigations including included fasting and 2-hour postprandial blood sugar, blood urea, serum creatinine, lipid profile, glycated hemoglobin, and microalbuminuria. Results: Patients with T2DM with or without ischemic stroke were found to have significantly higher prevalence of increased CIMT and a value greater than 0.8 mm was found to be associated with the occurrence of stroke. The mean carotid IMT of the group as a whole was 0.840 ± 0.2 mm. The mean carotid IMT was not significantly different between T2DM patients with or without ischemic stroke (1.06 ± 0.2 vs. 0.97 ± 0.26 mm, P = 0.08). However, the mean CIMT was significantly higher in diabetic subjects compared to healthy subjects (1.01 ± 0.28 mm vs. 0.73 ± 0.08, P = 0.006). Other parameters like higher age, smoking, hypertension, hyperlipidemia, low HDL cholesterol, the glycemic parameters and the duration of diabetes were independently and significantly related to CIMT. Conclusion: A high CIMT is a surrogate and reliable marker of higher risk of ischemic stroke amongst type 2 diabetic patients. Our study demonstrates the utility of carotid IMT as a simple non-invasive screening test for the assessment of atherosclerosis risk/prognosis in type 2 diabetics.

Sunil Kumar Kota

Papers

Renin–angiotensin system activity in vitamin D deficient, obese individuals with hypertension: An urban Indian study

Correlation of vitamin D, bone mineral density and parathyroid hormone levels in adults with low bone density.

Metabolic pancreatitis: Etiopathogenesis and management.

Effect of vitamin D supplementation in type 2 diabetes patients with pulmonary tuberculosis

Carotid intima media thickness in type 2 diabetes mellitus with ischemic stroke.