Consensus Statement on Management of Post-Prandial Hyperglycemia in Clinical Practice in India.

Postprandial hyperglycemia (PPHG) is a detrimental factor in the evolution of diabetes related complications. Numerous studies have established the role of PPHG in development of atherosclerosis and associated cardiovascular conditions. It is seen that management of PPHG can be more troublesome than fasting plasma glucose (FPG). Currently, there are various strategies both monitoring as well as therapeutic to control PPHG but there is no uniformity in practicing these strategies. In the absence of any standard guidelines, widespread variations in the management of PPHG are observed among physicians and diabetologists. The objective of this document is to set forth uniform guidelines to manage PPHG. This will not only result in optimal management and prevention of long term complications of diabetes but also better co-ordination and collaboration among the care providers. Moreover, an Indian perspective that can take into consideration the issues relevant to Indian patient pool will be effective. An expert committee comprising of prominent physicians and researchers associated with diabetes care provided their inputs to provide a basic platform for the formulations of guidelines. Their inputs were supplemented by extensive literature search to collect the relevant evidences. An initial draft was prepared which was reviewed by the core committee. Inputs from other experts were also sought and an initial guideline version was formulated that was presented in a conference, discussed and debated among experts. The guidelines on PPHG were then finalized and published.

Recent advances on the association of apoptosis in chronic non healing diabetic wound.

Generally, wounds are of two categories, such as chronic and acute. Chronic wounds takes time to heal when compared to the acute wounds. Chronic wounds include vasculitis, non healing ulcer, pyoderma gangrenosum, and diseases that cause ischemia. Chronic wounds are rapidly increasing among the elderly population with dysfunctional valves in their lower extremity deep veins, ulcer, neuropathic foot and pressure ulcers. The process of the healing of wounds has several steps with the involvement of immune cells and several other cell types. There are many evidences supporting the hypothesis that apoptosis of immune cells is involved in the wound healing process by ending inflammatory condition. It is also involved in the resolution of various phases of tissue repair. During final steps of wound healing most of the endothelial cells, macrophages and myofibroblasts undergo apoptosis or exit from the wound, leaving a mass that contains few cells and consists mostly of collagen and other extracellular matrix proteins to provide strength to the healing tissue. This review discusses the various phases of wound healing both in the chronic and acute wounds especially during diabetes mellitus and thus support the hypothesis that the oxidative stress, apoptosis, connexins and other molecules involved in the regulation of chronic wound healing in diabetes mellitus and gives proper understanding of the mechanisms controlling apoptosis and tissue repair during diabetes and may eventually develop therapeutic modalities to fasten the healing process in diabetic patients.

Blood pressure control with a single-pill combination of indapamide sustained-release and amlodipine in patients with hypertension: the EFFICIENT study.

OBJECTIVE: Despite antihypertensive treatment, most hypertensive patients still have high blood pressure (BP), notably high systolic blood pressure (SBP). The EFFICIENT study examines the efficacy and acceptability of a single-pill combination of sustained-release (SR) indapamide, a thiazide-like diuretic, and amlodipine, a calcium channel blocker (CCB), in the management of hypertension. METHODS: Patients who were previously uncontrolled on CCB monotherapy (BP≥140/90 mm Hg) or were previously untreated with grade 2 or 3 essential hypertension (BP≥160/100 mm Hg) received a single-pill combination tablet containing indapamide SR 1.5 mg and amlodipine 5 mg daily for 45 days, in this multicenter prospective phase 4 study. The primary outcome was mean change in BP from baseline; percentage of patients achieving BP control (BP<140/90 mm Hg) was a secondary endpoint. SBP reduction (ΔSBP) versus diastolic BP reduction (ΔDBP) was evaluated (ΔSBP/ΔDBP) from baseline to day 45. Safety and tolerability were also assessed. RESULTS: Mean baseline BP of 196 patients (mean age 52.3 years) was 160.2/97.9 mm Hg. After 45 days, mean SBP decreased by 28.5 mm Hg (95% CI, 26.4 to 30.6), while diastolic BP decreased by 15.6 mm Hg (95% CI, 14.5 to 16.7). BP control (<140/90 mm Hg) was achieved in 85% patients. ΔSBP/ΔDBP was 1.82 in the overall population. Few patients (n = 3 [2%]) reported side effects, and most (n = 194 [99%]) adhered to treatment. CONCLUSION: In patients who were previously uncontrolled on CCB monotherapy or untreated with grade 2 or 3 hypertension, single-pill combination indapamide SR/amlodipine reduced BP effectively--especially SBP--over 45 days, and was safe and well tolerated. TRIAL REGISTRATION: Clinical Trial Registry-India CTRI/2010/091/000114.

Promising role of ANGPTL4 gene in diabetic wound healing.

Diabetes mellitus (DM) is one of the severe metabolic disorders of carbohydrate metabolism worldwide. Developing countries are at higher risk of DM, and there is significant evidence that it is epidemic in many economically developing and newly industrialized countries. Among all other complications associated with DM, delayed wound healing is a major concern in diabetic patients. Wound healing is a natural healing process that starts immediately after injury. This involves interaction of a complex cascade of cellular events that generates resurfacing, reconstitution, and restoration of the tensile strength of injured skin. There are multiple factors responsible for delayed wound healing among which the contribution of DM has been well documented. The wound healing process is also delayed by the metabolic, vascular, neurological, and inflammatory alterations, which are well known in both type 1 and type 2 diabetes. Keratinocytes are crucial for wound re-epithelialization, and defects in directed migration of keratinocytes due to DM are associated with the delayed wound healing process. Many factors responsible for re-epithelialization have been identified, characterized, and well described; however, the genes responsible for the healing process have only partially been illustrated. This article will therefore focus on the efficacy of ANGPTL4 (angiopoietin-like 4) gene, which plays a novel role in keratinocyte migration during wound healing.

Clinical and imaging perspective and unanswered questions in a case of metronidazole induced encephalopathy.

We discuss the clinical and imaging perspective in a case of a 78-year-old male who developed slurring of speech and ataxia acute in onset for the last 3 days. During his hospital stay, he developed multiple episodes of focal seizures without secondary generalization involving the angle of mouth on the right side. The patient had ataxia and positive cerebellar signs. In the past, the patient was treated for amoebic liver abscess and had undergone percutaneous aspiration of abscess. The patient was prescribed oral metronidazole and was discharged. This time, the patient underwent magnetic resonance imaging examination, which revealed lesion highly suggestive of metronidazole-induced encephalopathy. The offending drug was discontinued immediately after which the patient improved clinically. A follow-up scan was performed after 12 days and showed complete resolution of lesions.

Oral mucosal involvement in visceral leishmaniasis.

Leishmaniasis affects both the visceral and cutaneous tissues in body. Oral Mucosal involvement in leishmaniasis is rare and is often overlooked. We present a case 17 year old boy from the north east region of Bihar who has a history of visceral leishmaniasis one year back, came to the department of oral surgery for treatment of persistent oral ulcers. Oral examination did not give any diagnostic information while systemic examination revealed enlarged spleen and low grade fever. Patient was screened for leishmaniasis by rK39 based immunochromatographic strip test which came to be positive. Biopsy of the ulcer as well as splenic and bone marrow aspirate confirmed the presence of leishmaniasis. Patient was administered Amphotericin B for 20 days following which significant clinical and haematological improvement followed.

Correlation of insulin resistance, beta cell function and insulin sensitivity with serum sFas and sFasL in newly diagnosed type 2 diabetes.

Pancreatic beta cell dysfunction and reduced insulin sensitivity are fundamental factors associated with glucotoxicity, lipotoxicity and oxidative stress in type 2 diabetic patients (T2DM). Diabetic milieu can induce apoptosis in several types of cells. The aim of present study was to compare circulating soluble apoptotic markers (sFas and sFas-L) with HOMA-IR, HOMA-%S, HOMA-%B in the serum of newly diagnosed T2DM and healthy subjects. For this study, 94 T2DM and 60 healthy subjects were enroled and evaluated for various parameters. Biochemical quantifications were performed with Syncron CX5 auto-analyzer. The levels of serum sFas-L, TNF-α and IL-6 were estimated by flowcytometry. The fasting serum insulin and sFas quantified by ELISA. HOMA-IR, HOMA-%S and HOMA-%B were calculated with HOMA calculator v2.2.2. The levels of TC, TG, LDL-C, VLDL-C were augmented and HDL declined significantly (P < 0.001) in diabetics. The levels of serum insulin, TNF-α, IL-6, sFas, HOMA-IR were raised (P < 0.001) and sFas-L, HOMA-%S and HOMA-%B were decreased significantly (P < 0.001) in T2DM subjects than healthy. In diabetics, serum sFas was positively correlated with HOMA-IR (r = 0.720, P < 0.001) and negatively with HOMA-%B (r = -0.642, P < 0.001) significantly while serum sFasL was negatively correlated with HOMA-IR (r = -0.483, P < 0.001) and positively with HOMA-%B (r = 0.466, P < 0.001) significantly. Further, the multivariate stepwise regression analysis shows that HOMA-IR contributes significantly to the variance of sFas and sFasL. Our findings suggest that the pancreatic beta cell dysfunction along with increased insulin resistance appears to be associated with apoptotic markers.

Hodgkin's Lymphoma Presenting as Alopecia.

Alopecia is a rare manifestation of Hodgkin's disease. It may be due to follicular destruction due to direct infiltration by the disease, or it may be a secondary or paraneoplastic manifestation. In this patient, hair loss, diffuse yperpigmentation, and generalized itching preceded other manifestations of the disease. The pattern of hair loss was diffuse and generalized in nature involving scalp, eyebrows, axilla, and groin. Subsequently, the patient was diagnosed to be a case of Hodgkin's lymphoma, based on clinical and histopathological features. Earlier reports on alopecia accompanying Hodgkin's disease have also been discussed. This case highlights the importance of keeping a high suspicion of an underlying malignancy in patients presenting with such cutaneous manifestations.

Correlation between IL-7 and MCP-1 in diabetic chronic non healing ulcer patients at higher risk of coronary artery disease.

Cytokines play an extremely important role in the pathogenesis of coronary artery disease (CAD) in which interleukin (IL)-7 is a major regulator of T-cell homeostasis which is conced in the stimulation of leukocyte-endothelial cell adhesion during inflammatory events. Circulating IL-7 is associated with activation of monocyte and natural killer cells, leading to enhanced production of inflammatory cytokines and chemokines observed in atherosclerosis and acute coronary syndromes. Plasma levels of IL-7, hs-CRP and monocyte chemoattractant protein (MCP)-1 were measured by an immunoenzymatic ELISA technique. Ninety neuropathic diabetic foot patients were divided into two groups: group B [those without CAD (n=45)] and group C [those with higher risk of CAD (n=45)]. Thirty-five healthy subjects were included as control (group H). Plasma concentration of IL-7, MCP-1 and hs-CRP were significantly higher in group C as compare with group H and B. Plasma IL-7 levels also showed significant positive correlations with plasma levels of hs-CRP and MCP-1. Abnormalities in lipid profile were also observed. In conclusion the positive correlation between plasma concentration of IL-7, MCP-1 and hs-CRP in diabetic foot patients observed herein, suggests a plausible role for IL-7 in the promotion of clinical instability in coronary artery disease.

Trichotillomania and dermatitis artefacta: a rare coexistence.

A 24-year-old pregnant female patient presented with complains of bilateral lower limb swelling and fever for 1 month. On examination, blood pressure was 144/94 mmHg along with pitting pedal edema. She had bizarre skin lesions, aligned longitudinally and distributed over the approachable site of the body with tapering ends and in various stages of healing. Lower limbs examination also revealed similar lesions with signs of cellulitis. Her scalp had short and distorted hair suggesting pulling and plucking. These skin lesions and the denial of self-infliction by the patient made us reach the diagnosis of dermatitis artefacta with trichotillomania. Psychotherapy was advocated along with conservative management of skin lesions. The patient improved and is under our follow up.

Atypical neurofibroma and osteosclerotic metastasis.

35-year-old male presented with multiple swellings in left leg, headache, weakness of limbs for 4 months, and blurring of vision for the last 15 days. On examination, he was pale, cachexic with generalized lymphadenopathy and lower motor neuron type weakness of limbs sparing right upper limb. Blood investigations showed anemia with high alkaline phosphatase. Chest radiograph revealed osteosclerotic metastatic lesion in humerus. Biopsy of leg lesion revealed atypical neurofibroma. Computed tomography (CT) of thorax revealed osteoblastic metastasis. Bone marrow aspiration showed cells with round to oval nuclei, fine granular chromatin with large central prominent nucleoli and eosinophilic cytoplasm with acini formation. Magnetic resonance imaging (MRI) of brain and spinal cord defined metastatic leptomeningeal deposits. Cerebrospinal fluid (CSF) cytology was positive for malignant cells. Gastroscopy showed an ulceroinfiltrative growth from stomach which on histopathology revealed diffuse adenocarcinoma. Palliative treatment was given with intrathecal methotrexate and systemic corticosteroid with chemotherapy. Patient's symptom improved drastically, but we lost him to followup.

Visceral leishmaniasis or systemic lupus erythematosus flare?

Systemic lupus erythematosus (SLE) is a multisystem disorder characterised by B-cell hyperactivity with production of multiple autoantibodies. Fever in SLE may be caused by disease exacerbation or by infection. We report a patient of SLE that was later complicated by fever, pancytopenia, and massive splenomegaly. Corticosteroid therapy for SLE might have masked the underlying infection at earlier stage. Despite negative results of rk-39 test and bone marrow biopsy, a very high suspicion for visceral leishmaniasis (VL) led us to go for direct agglutination test (DAT) and polymerase chain reaction (PCR) for leishmanial antigen that revealed positive results. Moreover, significant improvement in clinical and biochemical parameters was noted on starting the patient on antileishmanial therapy.

A rare case of Balo concentric sclerosis showing unusual clinical improvement and response with oral prednisolone.

The present report is a rare case of Balo Concentric Sclerosis. Most cases have either been diagnosed post mortem or have succumbed to the disease after being diagnosed ante mortem. In our case, the patient showed a dramatic response to treatment, and after a one-year follow-up, he was asymptomatic, with no relapses or residual effect of the illness.

Level of serum IL-12 and its correlation with endothelial dysfunction, insulin resistance, proinflammatory cytokines and lipid profile in newly diagnosed type 2 diabetes.

AIM: This study was an attempt to evaluate and correlate serum interleukin-12 (IL-12) with different circulating markers in newly diagnosed type-2 diabetes mellitus (T2DM) for possible progression of atherosclerosis. METHODS: For this study, we recruited 1968 family members of diabetics and 349 had abnormal glucose. Out of 349 subjects, 197 were T2DM as per American Diabetes Association guidelines and further investigated for cardiovascular abnormalities. 63 T2DM have high sensitive C-reactive protein (hsCRP)>3.0mg/l and cardiovascular complications. Overall, 150 subjects, 50 healthy, 50 T2DM (D1) and 50 T2DM with cardiovascular complications (D2) were enrolled and investigated for soluble markers. RESULTS: The levels of serum glucose, proinflammatory cytokines (IL-6, IL-12, tumor necrosis factor), endothelial dysfunction markers [vascular cell adhesion molecule-1 (VCAM-1), inter-cellular adhesion molecule-1 (ICAM-1), nitric oxide] and lipid abnormality were highest in D2 group. Correlation and regression study showed that IL-12 was dependent on hsCRP, insulin resistance, VCAM-1, ICAM-1 and lipids. The multivariate stepwise regression analysis demonstrates that hsCRP contributes significantly for variance of IL-12. CONCLUSION: This study reveals that, even first-time diagnosis of T2DM, subjects with higher insulin resistance and abnormal lipids have elevated IL-12, endothelial dysfunction and proinflammatory markers. Further increased hsCRP enhance IL-12 which up-regulate cardiovascular disease progression.

Relationship between oxidative stress and apoptotic markers in lymphocytes of diabetic patients with chronic non healing wound.

AIMS: Hyperglycemia causes generation of free radicals which leads to oxidative stress and apoptosis in various cells. The present study was undertaken to investigate the correlation between oxidative stress and apoptotic markers in lymphocytes of diabetic patients with chronic non healing wounds. METHODS: Thirty healthy, thirty uncontrolled type 2 diabetes mellitus (T2DM) and thirty uncontrolled T2DM with chronic, non healing, neuropathic diabetic foot patients were included in this study. Indices of oxidative stress inside the lymphocyte lysate were estimated by measuring content of superoxide dismutase (SOD), Catalase, Glutathione and malonaldialdehyde (MDA). Protein expression studies of pro and anti apoptotic markers were carried out to elucidate their possible involvement in diabetic context. RESULTS: SOD and MDA activity was significantly higher in the lymphocytes of diabetic patients having chronic, non healing diabetic wound as compared with healthy (p<0.001); whereas catalase and GSH activity was significantly reduced (p<0.001) in the same group. Expressions of pro apoptotic markers (Caspase-3, Fas and Bax) were significantly higher whereas reduced expression of anti-apoptotic marker (Bcl-2) were obtained in lymphocytes of diabetic and non diabetic individuals. CONCLUSIONS: Hyperglycemia confers pro apoptotic manifestations which are mostly through altered indices of oxidative stress within lymphocytic milieu.

Determinants of intravascular resistance in Indian diabetic nephropathy patients: a hospital-based study.

Aims and Objectives. Metabolic dysregulation has failed to explain clinical variability of patients with diabetic nephropathy and hence a renewed interest emerged in haemodynamic factors as determinant of progression and development of diabetic nephropathy. We therefore studied for various factors which can correlate with raised renal vascular resistance in diabetic nephropathy. Material and Methods. Renal vascular resistance was measured in patients with established and incipient diabetic nephropathy and compared with controls using noninvasive color Doppler examinations of intrarenal vasculature. Results. Renal vascular resistance correlated with age, duration of disease, GFR, serum creatinine, and stage of retinopathy. Renal vascular resistance was significantly reduced in patients on treatment with RAAS inhibitors and insulin, than those on OHA and antihypertensives other than RAAS inhibitors. Conclusion. The study implies that renal vascular resistance may help identify diabetics at high risk of developing nephropathy, and these set of patients could be candidates for RAAS inhibition and early insulin therapy even in patients without albuminuria.

Effect of selenium on connexin expression, angiogenesis, and antioxidant status in diabetic wound healing.

This study was done to analyze the effect of selenium on antioxidant status and expression of different connexins in diabetic wound healing. The levels of vascular endothelial growth factor, superoxide dismutase, lipid peroxide, and connexins were analyzed in wound tissues taken from diabetic and non-diabetic mice before and after sodium selenite administration. The mRNA transcript levels of Cx 26, 30.3, 31, 31.1, and 43 were significantly elevated in diabetic wounds as compared to the non-diabetic wounds. After selenium administration, the expression of connexins along with serum glucose decreases more significantly in diabetic wounds as compared to non-diabetic wounds. In diabetic wounds, the low levels of vascular endothelial growth factor and extracellular superoxide dismutase were restored to normal level following selenium administration. The lipid peroxidation decreased significantly in diabetic mice post-selenium administration. The histopathological analysis revealed that administration of selenium improves angiogenesis at the wound site. The results of this study demonstrate that selenium, acting as an essential component of the antioxidant system, normalizes the antioxidant status, and as an insulin mimetic compound, downregulates connexin expressions and induces angiogenesis. Together, these effects of selenium accelerate wound healing in diabetic conditions.