HNF1α upregulation and promoter hypermethylation as a cause of glucose dysregulation: a case-control study of Kashmiri MODY population.

AIM: HNF1α transcription factor regulates a network of genes involved in the development of ß-cells and also serves as a model for transcription defects in pancreatic ß-cells; mutations in this gene cause MODY. The goal of this study was to assess the promoter methylation and expression profile of the most common MODY causing gene, HNF1α, in Kashmiri MODY patients, as factors responsible for glucose dysregulation, as no such study had been performed on MODY patients in Kashmir previously. METHODS: The study included 85 Kashmiri subjects. Samples were extracted for DNA and RNA using standard protocols. The HNF1α promoter methylation profile was assessed by bisulfite conversion of the DNA followed by MSP, whereas qPCR was used for expression analysis. RESULTS: The expression of HNF1α was found to be upregulated (p value 0.0349*) in majority of MODY (60%) and T1D (72%) cases (p value 0.0349*). HNF1α expression was 1.33-fold higher in MODY cases with hypermethylated HNF1α promoters (p value 0.0360*). HNF1α expression was upregulated by 2.3-fold in MODY patients with HbA1c levels > 7% (p value 0.0025**). MODY cases with FBS levels > 7.7 mmol/l were upregulated by 0.646-fold than those with FBS levels ≤ 7.7 mmol/l (p value 0.0161*). CONCLUSION: In this study, we found that as glucose dysregulation progresses, blood FBS, RBS, and HbA1c levels rise, and that at higher levels, HNF1α expression rises as well. From the results obtained, we may conclude that HNF1α is strongly upregulated in MODY, thus indicating the deleterious effect of over expression of HNF1α gene on glucose regulation.

Cardiac structural and functional abnormalities in primary hyperparathyroidism.

PURPOSE: Studies on cardiac structural and functional abnormalities in primary hyperparathyroidism (PHPT) have yielded conflicting and inconsistent results. In this prospective case-control study, we sought to compare cardiac structure and function in symptomatic PHPT patients and controls. METHODS: One hundred consecutive symptomatic PHPT patients and 113 matched controls underwent echocardiographic evaluation by the same operator. RESULTS: Left ventricular mass index (LVMI) was significantly higher in patients as compared to controls, (median of 90.95 g/m2 vs 86.5 g/m2, p = 0.041). Patients had significantly lower early trans-mitral diastolic flow (E velocity) as compared to controls (57.13 ± 14.88 vs 64.76 ± 15.45 cm/s, p < 0.001). Patients also had significantly lower early to late mitral annular velocity (E/A) as compared to controls (0.98 ± 0.37 vs 1.10 ± 0.34, p 0.013). Patients had higher frequency of aortic valve calcification (29% vs 2.65%, p < 0.001), mitral annular calcification (23% vs. 4.42%, p < 0.001), myocardial and septal calcifications (25% vs none, p < 0.001) as compared to controls. Serum PTH, calcium and uric acid significantly correlated with calcifications. Serum calcium showed a negative correlation with E/A ratio. CONCLUSIONS: Symptomatic patients with PHPT have substantial cardiac structural and functional abnormalities. These abnormalities include elevated LVMI, diastolic dysfunction, and aortic valve, mitral annular, septal and myocardial calcifications. We strongly suggest and conclude that the evaluation of PHPT patients should not only include traditional end organs like bones and kidneys but also the cardiovascular system in the form of echocardiography to detect subclinical cardiac dysfunction so that the cardiovascular health of such patients can be optimized.

Primary hyperparathyroidism and pancreatitis.

PURPOSE: The true association between primary hyperparathyroidism (PHPT) and pancreatitis continues to be controversial. In this study, we present clinical data, investigative profile, management and follow-up of PHPT patients with pancreatitis and compare this group with PHPT patients without pancreatitis. METHODS: Records of 242 patients with PHPT managed at our center over 24 years were retrospectively analyzed for demographic and laboratory data. The diagnosis of pancreatitis was entertained in the presence of at least two of the three following features: abdominal pain, levels of serum amylase greater than three times the normal or characteristic features at imaging. RESULTS: Fifteen (6.19%) of the 242 consecutive patients with PHPT had had pancreatitis. Fourteen patients (93.3%) had acute pancreatitis (AP), while one patient had chronic calcific pancreatitis. Over half (8 of 14) of the patients with AP had at least two episodes of pancreatitis. Pancreatitis was the presenting symptom in 14 (93.3%) patients. None of the pancreatitis cases had additional risk factors for pancreatitis. PHPT patients with pancreatitis had significantly higher serum calcium and ALP than PHPT patients without pancreatitis. After successful parathyroidectomy, 14 patients had no further attacks of pancreatitis during a median follow-up of 16 months (range 2-41 months), while recurrence of pancreatitis was seen in one patient. CONCLUSIONS: We conclude that pancreatitis can be the only presenting complaint of PHPT. Our study highlights the importance of fully investigating for PHPT in any pancreatitis patient with high normal or raised serum calcium level, especially in the absence of other common causes of pancreatitis.

Causes of mortality in diabetes mellitus: data from a tertiary teaching hospital in India.

BACKGROUND: Mortality studies can show the relative contribution of diabetes to mortality in the total population, and they can provide important descriptions of the changes in causes and frequency of diabetes mortality over time. OBJECTIVE: To find the mortality pattern in people with diabetes admitted to a tertiary care hospital in a developing country, using underlying/contributory causes of death. METHODS: In this retrospective study, mortality trends among people with diabetes admitted to Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Kashmir, India were reviewed by screening the hospital records of all people with diabetes who died over the last 9 years, carrying forward earlier observations from the same centre. RESULTS: Of 234 776 people admitted to the centre during the review period, 16 690 (7.11%) died; 741 (383 men) of these had diabetes mellitus mentioned on the death certificate. The mean (SD) age at death for people with diabetes was 60.07 (13.62) years in men and 57.36 (13.40) years in women. The leading contributory causes of death were infections (40.9%), chronic renal failure (33.6%), coronary artery disease (16.9%), cerebrovascular disease (13.2%), chronic obstructive pulmonary disease (6.9%), acute renal failure (6.2%), malignancy (4.2%), hypoglycaemia (3.5%) and diabetic ketoacidosis (3.4%). The cause of death could not be ascertained in 2.8% of cases; in 52.9%, 36.3% and 8.0% cases one, two and three or more causes, respectively, were recorded as the cause of death. CONCLUSIONS: The aetiological spectrum of mortality in people with diabetes at this Indian centre continues to be dominated by infections and renal failure, which is different from that in the developed world, where coronary artery disease and cerebrovascular disease are the principal causes of death in people with diabetes.

Vitamin D status in apparently healthy adults in Kashmir Valley of Indian subcontinent.

BACKGROUND: The worldwide prevalence of vitamin D deficiency is reported to be high. OBJECTIVES: To assess the vitamin D status in apparently healthy adults in Kashmir valley by measuring serum 25-hydroxyvitamin D (25 (OH) D). METHODS: 92 healthy natives (64 men and 28 non-pregnant/non-lactating women, aged 18-40 years), residing in Kashmir for at least last 5 years and not having any suggestion of systemic disease, were selected for this study. The samples were collected throughout the year in both summer and winter months. Vitamin D deficiency was defined as a serum 25 (OH) D concentration of <50 nmol/l and graded as mild (25-50 nmol/l), moderate (12.5-25 nmol/l) and severe (<12.5 nmol/l). RESULTS: Body mass index, total energy intake, and other nutritional parameters were comparable among subjects in different groups. Overall 76 (83%) of the subjects studied had vitamin D deficiency--25%, 33%, and 25% had mild, moderate, and severe deficiency, respectively. 49 of the 64 males and all but 1 of the 28 females were vitamin D deficient. The prevalence of vitamin D deficiency ranged from 69.6% in the employed group to 100% in the household group. Vitamin D deficiency was equally prevalent in subjects from rural and urban areas. Serum calcium and phosphorus values were comparable in subjects with and without vitamin D deficiency, while daily intake and urinary excretion of calcium were significantly lower in the former. Vitamin D deficient subjects had a significantly lower mean weekly exposure to sunlight. CONCLUSIONS: In spite of abundant sunlight, healthy individuals in Kashmir valley are vitamin D deficient, particularly women. Serum 25 (OH) D concentrations are significantly related to sun exposure.

Presentation and outcome of emphysematous renal tract disease in patients with diabetes mellitus.

BACKGROUND: Emphysematous renal tract disease (ERTD) is a rare necrotizing infection of the renal parenchyma and urinary tract caused by gas-producing organisms. ERTD deserves special attention because of its life-threatening potential. OBJECTIVES: To study the clinical features, radiological classification and prognostic factors of ERTD; and to compare the modalities of management and the outcome among the various radiological classes of ERTD. PATIENTS AND METHODS: Twenty consecutive patients with diabetes and ERTD, seen over last 3 years in a tertiary care institute of north India, were included in the study. All patients were subjected to computerized tomography (CT) after initial diagnosis by ultrasonography. They were classified into 5 classes as previously described. All patients included in the study were conservatively managed with appropriate antibiotics and/or percutaneous drainage or surgery if required. RESULT: Mean age (+/- SD) of these subjects was 54.4 +/- 20.6 years; duration of diabetes mellitus 8.6 +/- 5.8 years, and duration of symptoms related with ERTD ranged from 3 days to 3 months. Two patients had isolated emphysematous cystitis, 13 patients had emphysematous pyelonephritis (EPN), 3 had both EPN and cystitis, and 1 patient had EPN with cholecystitis, and 1 patient had EPN with pyomyositis. Only 7 (35%) patients had a history of pneumaturia. Escherichia coli was the commonest microorganism. The radiological distribution in 18 (2 had isolated cystitis) patients with EPN was: 2 patients had class 1; 1 had class 2; 2 had class 3A; 11 had class 3B, and 2 had class 4. Of 20 patients 11 (55%) survived. However, those patients who died had severe EPN based on radiological class (6 had class 3B and 1 had class 4). There was no significant difference between the survivor and non-survivor groups with respect to age, gender, duration of diabetes mellitus, duration of symptoms, serum creatinine level, total leukocyte count, hemoglobin, platelet count and culture positivity. CONCLUSION: Computerized tomographic class 3B or 4 is the most reliable predictor of outcome in patients with ERTD.

Ultrasonography in detection of single and multiple abnormal parathyroid glands in primary hyperparathyroidism: comparison with radionuclide scintigraphy and surgery.

BACKGROUND: Among the parathyroid imaging techniques, ultrasonography (USG) has the advantage of convenience, easy availability and low cost. OBJECTIVE: To study the role of USG in localization (side and/or site) of abnormal parathyroid glands in primary hyperparathyroidism (PHPT) and to compare with radionuclide scintigraphy and the 'gold standard', surgery. METHODS: Forty-six consecutive patients undergoing USG of the anterior neck for a diagnosis of PHPT in whom a nuclear scan (technetium-99m sestamibi and/or thallium-201/technetium-99m pertechnetate scintigraphy) was also performed, were studied. The results of imaging were independently interpreted and correlated with reference to surgical findings. RESULTS: Forty-six patients had 52 abnormal parathyroid glands on surgical exploration and surgery was successful in all but one. Forty-one patients had a single adenoma, four had multigland disease and one had a paraganglioma. USG correctly localized the abnormal gland in 30 (73%) and scintigraphy was positive in 40 (98%) out of 41 patients with a single adenoma as confirmed on surgical exploration. Scintigraphy showed a positive concordant test in all 30 patients with a single abnormal gland detected on USG and picked up 10 out of 11 abnormal glands where USG was negative. The sensitivity and positive predictive value of USG for detecting a single abnormal gland was 73% and 100%, respectively, whereas the sensitivity and positive predictive value for scintigraphy was 98%. In patients with multigland disease, USG missed 3 (30%) out of 10 and scintigraphy missed 6 (60%) out of 10 abnormal parathyroid glands as confirmed on surgical exploration (P < 0.05). However, in two patients who had ectopic parathyroid gland, both the modalities localized the lesion in one (paraganglioma), whereas in the other neither test was helpful (left retro-esophageal). CONCLUSION: USG is a convenient, affordable and useful modality to localize abnormal enlarged parathyroid glands in the majority of patients with PHPT. However, when USG is negative, scintigraphy is complementary to it.

Juvenile hyperthyroidism: an experience.

OBJECTIVE: To analyze the clinical profile of juvenile hyperthyroidism at presentation, their treatment outcome; predictors of remission and relapse. METHODS: Retrospective analysis of medical records of 56 patients with juvenile hyperthyroidism seen over a period of 16 years. A cohort of 38 females and 18 males with mean (+/-SD) age of 14.9 +/- 3.4 years (range 3 to 18 years) was analyzed. RESULTS: Majority of patients was in the age group of 12-16 years. Common symptoms observed at presentation were weight loss (82.1%), excessive sweating (78.6%), heat intolerance (76.8%), increased appetite (73.2%) and diarrhea in 48.2%. In addition, accelerated linear growth was observed in 7.1% of patients. Goiter was present in 98.2% of children; 94.5% of which was diffuse and 4.8% was multinodular. The mean ((+/-SD) T3 was 4.8 +/- 3.4 ng/mL (N, 0.6-1.6), T4 was 218 +/- 98 ng/mL (N, 60-155) and TSH was 0.44 +/- 0.36 (N, 0.5-5.5 microIU/mL). TMA positivity seen in 36.9% of patients. All patients were treated with carbimazole; subsequently 4 patients required thyroidectomy and one required radioactive iodine ablation. Mean (+/-SD) duration of follow-up in our patients was 4.9 +/- 3 years, ranging between 1.6 to 16 years and mean (+/-SD) duration of treatment was 34.4 +/- 22.6 months (range 12 to 120 months). Mean (+/-SD) duration to achieve euthyroidism was 5.2 +/- 4.7 months, ranging between 1-33 months. On intention to treat analysis, remission with carbimazole was achieved in 47.6%, remaining patients failed to achieve remission with drug treatment. CONCLUSION: Graves disease is the commonest cause of juvenile hyperthyroidism. Carbimazole is safe, effective, cheap, and easily available form of therapy. It is occasionally associated with serious side effects but requires prolonged follow up.

Efficacy of once- or twice-daily extended release metformin compared with thrice-daily immediate release metformin in type 2 diabetes mellitus.

BACKGROUND: The extended-release formulation of metformin (MXR) prolongs drug absorption in the upper gastrointestinal tract and permits once-daily dosing in patients with type 2 diabetes mellitus (T2DM). This newer formulation may enhance patient compliance with oral therapy compared to conventional immediate-release metformin (MIR) in T2DM. OBJECTIVES: To analyse whether a switch from thrice daily MIR to once or twice daily MXR wouldachieve comparable degrees of glycemic control in patients with type 2 diabetes mellitus (T2DM). METHODS: We conducted an open study of the efficacy and tolerability of MXR in 40 patients with T2DM who had achieved moderate or good glycemic control with MIR alone or in combination with other antihyperglycemic agents. After a lead in period of 3 months patients were switched over to a specific brand of MIR at baseline (Visit 0). Patients were subsequently followed for 4 more visits. These visits were done monthly, after taking MIR in a dose of 1-2 g/day (Visit 1); MXR as a single dose at dinner but 0.5 g less than baseline dose of MIR (Visit 2); MXR, 1-2 g/day as a single dose at bedtime, with strength same as that of baseline dose of MIR (Visit 3); and MXR, 1-2 g/day in two divided doses keeping dose same as baseline MIR (Visit 4). Glycemic control was assessed by a four-point glucose profile (fasting and three postprandial levels) at each visit. RESULTS: At visit 2, when patients had been on 500 mg lesser dose of MXR for 1 month, glucose profile worsened. However, glycemic control, at visit 3, returned to earlier levels when dose of MXR was increased back to original dose. Overall the MXR formulation was well tolerated with minor gastrointestinal adverse effects, reported by only 3 patients. CONCLUSION: Patients with T2DM who had been receiving thrice-daily MIR achieved comparable glycemic control when therapy was switched to once- or twice-daily MXR at the same total daily dose.

Clinical and etiological profile of hyperprolactinemia--data from a tertiary care centre.

OBJECTIVE: To study the clinical presentation and etiology of hyperprolactinemia, a common disorder encountered in endocrine practice. METHODS: We analyzed the clinical data, hormone profile and imaging reports of 187 females with documented hyperprolactinemia, over a period of 6 years (5 years retrospective analysis and one year prospective study). RESULTS: Majority of the 187 subjects studied presented in 3rd or 4th decade. Galactorrhoea was the commonest presenting symptom occurring in 159 subjects (85%), followed by amenorrhea in 68.9%; both amenorrhea and galactorrhea were seen in 45.4%. A microprolactinoma was demonstrated in 67 patients (35.8%), a nonfunctioning pituitary macroadenoma with stalk hyperprolactinemia occurred in 30 patients (16%) and polycystic ovarian disease was documented in 24 (12.8%). In 52 patients (27.8%) no apparent cause could be ascertained. CONCLUSIONS: Syndrome of amenorrhea and/or galactorrhea is the commonest presentation in hyperprolactinemia. Microprolactinoma was the most frequent identifiable etiology followed by idiopathic and stalk hyperprolactinemia in our series.

Reversibility of thyrotroph hyperplasia after L-thyroxine replacement therapy in patients with juvenile primary hypothyroidism.

Thyrotroph cell hyperplasia in primary hypothyroidism though well described is often not discussed as it remains clinically silent. This hyperplasia in long standing juvenile primary hypothyroidism presenting as 'pituitary tumor' is very uncommon. We report four patients with juvenile primary hypothyroidism, who were detected to have sellar/suprasellar masses on imaging performed for unrelated symptoms, and complete resolution in three of them after L-thyroxine replacement therapy.

Prevalence and pattern of sick euthyroid syndrome in acute and chronic non-thyroidal illness--its relationship with severity and outcome of the disorder.

BACKGROUND: Non-thyroidal illness is a common cause of alterations in thyroid hormone economy in absence of underlying intrinsic thyroid disorder. OBJECTIVE: To study the prevalence and pattern of alterations in thyroid hormone economy in various non-thyroidal illnesses in our region and also to correlate these alterations with the severity and outcome of the non-thyroidal illness. MATERIAL AND METHODS: We analyzed circulating T3, T4, TSH in 382 patients with non-thyroidal illness (285 acute and 97 acute on chronic) and correlated the alterations with severity and outcome of the non-thyroidal disorder. The patients had one or more organ failure at the time of enrollment to the study. The hormones were estimated at the onset of sickness, and at 3rd and 24th week. T3, T4 and TSH in 75 age and sex matched euthyroid subjects were taken as controls. RESULTS: T3 (mean +/- SEM) was significantly reduced at the onset of illness, in both acute and chronic patient groups (1.61 +/- 0.05 nmol/l) compared to that in the controls (3.17 +/- 0.06 nmol/l). In spite of clinical improvement in most instances, T3 continued to remain low in the 3rd week (1.49 +/- 0.11 nmol/ l) but increased (2.14 +/- 0.09 nmol/l) in 24th week. Low T3 was found in 93 (32.6%) cases with acute illness in 20 (20.6%) cases with chronic illness. A combination of low T3 and T4 was found in 35 (12.3%) of cases with acute and 15 (15.5%) with chronic illness. Although serum TSH showed noticeable fall and rise in some individuals, no significant difference in mean TSH was observed during any period of illness compared to that in the controls. Severity of illness correlated with decrease in T3 (r=0.58) and T4 (r=0.38). A low T3 and T4 with low or undetectable TSH were associated with increased mortality. At the onset of acute illness low T3 was seen in 113 (29.6%, low T3 -low T4 in 50 (13.1%), high T4 in 28 (7.3%) lowT3-lowT4- low TSH in 10 (2.6%) and low T4 alone in 4 (1%) patients. Fifty one 1 (13.4%) of our patients demonstrated alterations in TSH in presence of normal T3 and T4-26 patients had decreased TSH while as 25 had increased TSH. Of 118 patients who followed at 24 weeks, 11 (9.3%) had low T3, 7(5.9%) had low T3- low T4 and 13 (11%) had elevated TSH. CONCLUSION: Pattern and prevalence of sick euthyroid syndrome in this part of the world, a recognized iodine deficient region, appears to be similar to that reported elsewhere. Important finding in our study was higher percentage of TSH elevation, which we believe to reflect the underlying iodine deficiency state of our community. Besides a significant number of subjects persisted with alterations in thyroid functions even after 6 months of therapy. Though the severity of thyroid hormone derangement correlated with severity of sickness, the derangement was similar in acute vs. acute on chronic nonthyroidal illnesses.

Diffuse abdominal lipomatosis.

We report a 22-year male who developed progressive distension of abdomen, clinically diagnosed as ascites. A diagnosis of abdominal lipomatosis was made on the basis of CT evidence of excessive fatty tissue in abdominal cavity which was confirmed on laparotomy.

Response of regimens of insulin therapy in type 2 diabetes mellitus subjects with secondary failure.

OBJECTIVE: To find the response of various regimen of combination therapy (Insulin and Glibenclamide) in type 2 diabetes mellitus subjects who failed to respond to maximum doses of glibenclamide (GBC) plus phenformin. METHODS: A total of 188 subjects with secondary sulfonylurea failure who failed to respond to maximum doses of GBC and phenformin were randomised to receive one of the four regimens. Group A (50 patients) received two doses of insulin; Group B (49 patients) received two doses of insulin and GBC 20 mg/day; Group C (43 patients) received morning dose of insulin with GBC 20 mg/day; and Group D (46 patients) received evening dose of insulin with GBC 20 mg/day. Insulin dose was adjusted to achieve an acceptable blood glucose control. Control of diabetes was revaluated at three months post-treatment period. RESULTS: Age, duration of diabetes, weight, body mass index (BMI) and biochemical parameters were comparable in all four groups at admission. Dose of insulin was 0.83 +/- 0.07, 0.86 +/- 0.06, 0.46 +/- 0.04 and 0.39 +/- 0.03 units/Kg/day in groups A, B, C and D, respectively. Comparing groups A and B, we found that the dose of insulin (IU/kg/day) required to achieve acceptable fasting blood glucose (FBG) did not differ significantly. Similarly, comparison between Groups C and D did not reveal any significant difference in insulin dose. Mean hospital stay required to achieve an acceptable FBG was 8.42 +/- 0.34, 11.95 +/- 1.11, 8.59 +/- 0.61 and 7.10 +/- 0.48 days in groups A, B, C and D, respectively (p = 0.013). On comparing the four treatment regimens, at three months follow-up, there was a significant increase in bodyweight in Group C; also there was an increase in fasting blood glucose in all the groups except in Group D. CONCLUSIONS: Continuation of GBC in type 2 diabetes mellitus subjects who fail to respond to maximum doses of GBC plus phenformin and who need two doses of insulin for control has no added advantage over giving insulin alone. In subjects controlled on a single dose of insulin with glibenclamide it is preferable to give an evening dose rather than a morning dose.

Postpartum thyroiditis in India: prevalence of postpartum thyroiditis in Kashmir Valley of Indian sub-continent.

Various studies have reported a spectrum of thyroid dysfunction in the postpartum period. Postpartum thyroiditis is a syndrome of thyroid dysfunction that occurs in the first year after parturition. Prevalence of postpartum thyroiditis has been reported to vary from 3 to 6 percent in different regions of the world. Kashmir Valley is inhabited by a relatively homogeneous racial group and the Valley has been documented to have significant iodine deficiency. We studied the prevalence and pattern of postpartum thyroiditis in an urban region of this Valley. 120 women were registered within first month of postpartum period for the study along with one hundred controls. Of these 120 women, 104 reported for follow-up at 3 months postpartum and 106 reported for follow-up at 6 months postpartum. Initial and subsequent clinical details at follow-up were recorded on a pre-determined questionnaire. Overall, postpartum thyroiditis (PPT) was seen in 8 (7%) study subjects. Of these 8 patients with PPT, 4 had biochemical evidence of thyrotoxicosis at first month, 3 developed biochemical thyrotoxicosis at 3-month follow-up while as one study subject developed thyrotoxicosis at 6 months. Most of these subjects were antithyroid antibodies (anti-microsomal and anti-thyroglobulin) positive. We conclude that iodine deficient status of the community doesn't seem to influence the incidence of PPT.

Clinical and aetiological profile of early onset diabetes mellitus: data from a tertiary care centre in the Indian subcontinent.

BACKGROUND: Type 2 diabetes mellitus (DM) in youth is emerging as a serious clinical entity and its incidence has increased over the years. AIM: To analyse the causes of DM in the age group of <40 years of age. SETTINGS AND DESIGN: Tertiary care centre; retrospective analysis of data from January 1990 to December 1999. SUBJECTS AND MATERIAL: Analysis of data of all the subjects of DM in whom disease started before the 40th birthday. RESULTS: 724 subjects were detected to have diabetes mellitus before their 40th birthday. Of these, 205 had Type 1, 174 had Type 2 and 48 had fibrocalculous pancreatic diabetes. Males outnumbered in Type 1 and fibrocalculous pancreatic diabetes while as females in Type 2 diabetes mellitus. Chronic complications were more common in Type 2 diabetes mellitus. CONCLUSION: Type 2 diabetes mellitus is becoming an important cause of diabetes in subjects with onset of disease at younger age.

A critical evaluation of signs and symptoms in the diagnosis of Addison's diseases.

OBJECTIVES: To determine the usefulness of clinical symptoms and signs in the diagnosis of Addison's disease. METHODOLOGY: A retrospective, hospital based study from analysis of case records of over 12 years period (1988-1999). Individual or groups of signs and symptoms in 66 patients of confirmed Addison's diseases were compared with 76 subjects with normal ACTH stimulation test, when clinical presentations were similar. RESULTS: Age spectrum of the two groups was similar. Signs and symptoms like weakness, weight loss, gastro-intestinal disturbances, skin/mucosal pigmentation and blood pressure were not statistically different between the two groups. Similarly blood glucose, sodium and potassium were not different between the two groups. Combination of three or more symptoms/signs had a high predictive value of diagnosing the disease than any individual or a combination of < 3 signs/symptoms (P=0.033). CONCLUSIONS: Combination of skin and mucosal pigmentation with gut disturbances and weight loss carried high predictive value in diagnosis of Addison's disease, while individual sign and symptom has poor differentiating value.