Arundhati G Diwan

Diabetes and Complications: Cellular Signaling Pathways, Current Understanding and Targeted Therapies.

Diabetes is a metabolic disorder and over the past decades, it has become a major cause of morbidity and mortality affecting the youth and middle-aged as it is the fourth leading cause of disease related to death. In both type 1 and type 2 diabetes the severe pathogenesis cause micro vascular complications: nephropathy, retinopathy, neuropathy and macro vascular complications: cardiovascular disease, heart attacks and stroke. Under hyperglycemia, activation of different signaling mechanisms such as an increased polyol pathway, advanced-glycation end product formation, activation of Protein Kinase C and hexosamine pathway leads to the over expression of reactive oxygen species and causes pathogenesis of diabetic complications. It is necessary to understand these pathways in diabetic complications causing damage to the secondary system of the body. In the past decade the understanding of these biochemical changes has increased tremendously and various molecules have been exploited as therapeutic targets for diabetic complications as better therapeutic approach. In this review, a brief overview about diabetes mellitus and chronic complications with their current understandings of cellular/molecular mechanisms and targeted therapies along with novel therapeutic strategies is discussed.

Clinical profile of the spectrum of multiple myeloma in a teaching hospital

Aim: To analyze the clinical and laboratory features of multiple myeloma (MM). Settings and Design: A cross-sectional study of 20 newly diagnosed patients with MM over a period of 1 year in a tertiary health-care center. Materials and Methods: Based on Salmon-Durie criteria, newly diagnosed 20 patients of MM were selected for the study. Routine hematological and biochemical investigations, bone marrow examination, serum protein electrophoresis and urine for Bence Jones protein were done. Radiological investigations conducted to look for osteolytic lesions, extramedullary involvement and other pathologies. Results: Out of total 20 patients, 10 were males and 10 were females with sixth decade as the common age group at presentation. Common clinical symptoms were bone pains, localized body swelling, fever, generalized weakness and fatigue and motor weakness of lower limbs. Clinical examination revealed pallor in 80% patients, bony tenderness in 85% patients and 55% patients presented with infections. All patients had a presence of M band on serum protein electrophoresis, whereas 30% patients had urinary Bonce Jones protein positive. Among skeletal system spine and skull were the common sites of involvement 60% and 55%, respectively. Nearly, 85% patients had osteolytic lesions. Conclusions: Among 20 patients; various clinical presentations observed were infections, renal impairment, paraplegia and extramedullary plasmacytosis in addition to anemia and bony pains.

Relationship between plasma glycation with membrane modification, oxidative stress and expression of glucose trasporter-1 in type 2 diabetes patients with vascular complications

BACKGROUND OF STUDY Enhanced protein glycation in diabetes causes irreversible cellular damage through membrane modifications. Erythrocytes are persistently exposed to plasma glycated proteins; however, little are known about its consequences on membrane. Aim of this study was to examine the relationship between plasma protein glycation with erythrocyte membrane modifications in type 2 diabetes patients with and without vascular complications. METHOD We recruited 60 healthy controls, 85 type 2 diabetic mellitus (DM) and 75 type 2 diabetic patients with complications (DMC). Levels of plasma glycation adduct with antioxidants (fructosamine, protein carbonyl, β-amyloids, thiol groups, total antioxidant status), erythrocyte membrane modifications (protein carbonyls, β-amyloids, free amino groups, erythrocyte fragility), antioxidant profile (GSH, catalase, lipid peroxidation) and Glut-1 expression were quantified. RESULT Compared with controls, DM and DMC patients had significantly higher level of glycation adducts, erythrocyte fragility, lipid peroxidation and Glut-1 expression whereas declined levels of plasma and cellular antioxidants. Correlation studies revealed positive association of membrane modifications with erythrocyte sedimentation rate, fragility, peroxidation whereas negative association with free amino groups, glutathione and catalase. CONCLUSION Our data suggest that plasma glycation is associated with oxidative stress, Glut-1 expression and erythrocyte fragility in DM patients. This may further contribute to progression of vascular complications.

Acromegaly presenting as Diabetic ketoacidosis

Dear Sir, An 18 years female, presented with acute onset nausea and vomiting for 8 to 10 h. Examination revealed a dehydrated patient with Kussmaul’s breathing, tachycardia, tachypnoea, and normal blood pressure. Investigations revealed random blood sugar of 492 mg/dl metabolic acidosis and ketonuria. Patient gave a history of severe headache, polyuria and polydipsia since past 7 to 8 months as well as increase in hand size and foot size leading to difficulty in wearing bangles and footwear. She had acanthosis nigricans in the neck region (Fig. 1). Diagnosis of Diabetic ketoacidosis was made primarily keeping in mind that she may be also a case of Acromegaly. Patient was started on insulin, 90 units per day. Urine ketones turned negative in 12 h. Her serum Insulin Like Growth Factor 1 (IGF 1) was 927.00 ng/ml (normal range 163–584 ng/ml) and other hormonal profile was normal. Magnetic resonance imaging of brain showed a pituitary macroadenoma (Fig. 2), confirming diagnosis of acromegaly. Transsphenoidal surgical resection was done and histopathological report revealed an eosinophilic adenoma of the pituitary gland. Our 18 years patient had eosinophil adenoma, most of which give rise to acromegaly between 30 and 50 years of age [1]. Impaired glucose tolerance is present in about half the cases while overt diabetes mellitus develops in about 10–15 % [2]. Diabetic Ketoacidosis (DKA) is a rare finding in acromegaly. GH and IGF-1 excess can induce resistance directly in the liver, adipose tissue and muscle, resulting in increased endogenous glucose production, decreased muscle glucose uptake Fig. 1 Acanthosis nigricans in the neck region

Distal renal tubular acidosis and quadriparaesis in Sjögren's syndrome: A cunning congregate

Sjogrens syndrome (SS) is a chronic autoimmune disease, chiefly affecting the exocrine glandular function of salivary glands and lacrimal glands. Rarely, it involves the kidneys, central and peripheral nervous system, muscloskeletal apparatus and lungs. We report a rare constellation of SS with distal renal tubular acidosis and quadriparaesis in a young female. History of quadriparaesis was acute, with rapid progression. Supplementary treatment for severe hypokalemia was instituted at the earliest, lest the patient develop respiratory muscle weakness. Concomitantly, metabolic acidosis with alkaline urine was suspected and subsequently investigated. Eventually, this was attributed to impaired renal acidification of urine in the distal tubules. History of dryness of eyes and mouth since 6 months justified salivary gland biopsy. The results yielded a lymphocytic infiltrative pathology strongly favoring SS. The patient benefited from prompt potassium replacement therapy and had complete resolution over the next week. Supportive treatment for predictable manifestations was continued along with potassium supplements.

An unusual case of fever and abdominal pain

Ascariasis is one of the commonest parasitic infestations in tropical countries. Main symptoms are pain in abdomen, weight loss, diarrhea and passage of worms in stool. If acute, it may present as intestinal obstruction, perforation, cholangitis, appendicitis and pancreatitis. The incidence of hepato-biliary ascariasis is probably underestimated. We report a case which presented to us with fever, abdominal pain and weight loss of a months duration, mimicking abdominal tuberculosis. On investigations, patient was found to have ascariasis of gall bladder, terminal ileum, caecum and appendix, causing simultaneous inflammation of all these structures.