Thrombotic Thrombocytopenic Purpura: A Tale of Two Cases.

Microangiopathic hemolytic anaemia, thrombocytopenia, renal failure, neurologic abnormalities, and fever form the pentad of thrombotic thrombocytopenic purpura (TTP). Early diagnosis is crucial because TTP responds well to plasmapheresis therapy but is associated with substantial mortality if left untreated. A substantial percentage of patients with TTP used to die from systemic microvascular thrombosis in the brain and the heart. However, since plasma exchange therapy became a mainstay in the treatment of TTP, mortality has reduced considerably. Diagnosing TTP can be difficult due to the vast range of symptoms and the absence of clearly defined diagnostic criteria. Hemolytic uremic syndrome and disseminated intravascular coagulation are a close differential of TTP. Here we report two patients with TTP who achieved remission when treated with steroids, plasmapheresis and were free of disease relapse till about two months during follow-up in the outpatient department.

Changes in ß-Cell Function in Offspring of Type-2 Diabetic Patients, as per Fasting and Two-Hour Plasma Glucose Levels.

Background The changes in ß-cell function in high-risk populations who are apparently in the normal glucose tolerant stage are still under investigation for designing earlier prevention strategies. This study analyzes changes in ß-cell function and insulin sensitivity across fasting and two-hour glucose categories spanning normal glucose tolerance (NGT) to impaired glucose tolerance (IGT), in offspring of subjects with type-2 diabetes mellitus (T2DM) compared to the controls without a known family history of T2DM. Methods Offspring of T2DM patients (cases) and individuals without a family history of T2DM (controls) were the subjects for this cross-sectional study. All participants underwent a 75 g oral glucose tolerance test and blood samples were collected for plasma glucose, insulin, C-peptide and proinsulin, at zero, 30, 60, and 120 minutes.  Results A total of 358 cases (age 23.0 ± 10.8 years, 54% males) and 287 controls (age 28.4 ± 8.10 years, 65% males) were the subjects of this study. Cases and controls were divided into subgroups based on fasting and two-hour glucose categories spanning NGT to IGT. Compared to the reference category of controls (< 80 mg/dL for fasting glucose and < 84 mg/dL for two-hour glucose), cases with IGT had ~60% decline in both ß-cell compensation (as measured as disposition index {0-120}) and insulin sensitivity (as measured as whole-body insulin sensitivity index {0-120}); adjusted for age, gender, and body mass index. From lower to higher fasting and two-hour glucose categories, there was a continuous and significant decline in ß-cell compensation in both cases and controls. Significant reduction in first-phase insulin secretion, as measured as insulinogenic (0-30) index, was only observed among two-hour glucose categories, not among the fasting glucose categories. In the transition from late NGT cases to IGT cases, there was a significant decline in ß-cell compensation, first-phase insulin secretion (more prominent than a decline in overall ß-cell secretion) and the changes in whole-body insulin sensitivity were not statistically significant. Conclusions The decline in ß-cell compensation was continuous and significant in offspring of subjects with type-2 diabetes and controls without a known family history of diabetes from early normal glucose tolerant ranges to impaired glucose tolerant ranges. Compared to the strictest glucose controlled category of controls, approximately 60% decline was observed in ß-cell compensation and insulin sensitivity, in impaired glucose tolerant offspring of subjects with type-2 diabetes mellitus.

Effect of Different Insulin Response Patterns During Oral Glucose Tolerance Test on Glycemia in Individuals with Normal Glucose Tolerance.

BACKGROUND: Research is still going on for detecting the earliest glucose homeostasis derangements in individuals, which is crucial for the prevention of glucose intolerance. This cross-sectional study analyzes different insulin response patterns during the oral glucose tolerance test (OGTT) and their implications on glycemia in normoglycemic individuals. SUBJECTS AND METHODS: The sample frame was the "Offspring of Individuals with Diabetes Study" database. All participants underwent OGTT. Blood samples were collected at 0, 30, 60, and 120 min for measurement of insulin, C-peptide, and proinsulin levels. Normal glucose tolerant individuals were selected for analysis. RESULTS: Four hundred fifty subjects (mean age, 25 years) were included and divided into two groups according to timing of plasma insulin peaking during OGTT: Group 1, peaking at 30 min; and Group 2, peaking at 60 or 120 min. Body mass index (BMI) and insulin resistance were comparable between the groups; however, Group 2 showed a significantly higher 60- and 120-min glucose level and lower disposition index. Based on the magnitude of the insulin levels, Group 1 was subdivided into Group N (normal pattern) and Group E (exaggerated pattern) with a 30-min insulin cutoff of 74 µU/mL (Group E, ≥74 µU/mL). Group 2 was subdivided into Group DL (delayed and limited pattern; 60-min insulin <73.0 µU/mL and 120-min insulin <80.0 µU/mL) and Group DE (delayed and exaggerated pattern; 60-min insulin ≥73.0 µU/mL or 120-min insulin ≥80.0 µU/mL). Group DE showed a significantly higher area under the curve (AUC) of glucose compared with the other groups and had a lower disposition index and high-density lipoprotein levels. Group DL had significantly lower insulin resistance and BMI compared with Group E but showed a similar AUC of glucose. CONCLUSIONS: A delayed insulin pattern was associated with higher postprandial glucose levels. Individuals with delayed and exaggerated insulin secretion may have a higher risk for glucose intolerance.

Insulin response to oral glucose in healthy, lean young women and patients with polycystic ovary syndrome.

BACKGROUND AND AIM: Insulin resistance and consequent hyperinsulinemia are common among patients with polycystic ovary syndrome (PCOS). Ethnicity and dietary habits affect insulin levels. There is little published information from India on insulin levels in PCOS patients. Thus the present study aimed to determine the insulin response to oral glucose in women with PCOS and healthy women. METHODS: In a case-control study design, women with PCOS and lean healthy women without a family history of diabetes mellitus underwent oral glucose tolerance testing. Samples were collected at 0, 1 and 2 h after glucose ingestion. RESULTS: Two hundred and eighty-five women with PCOS and 27 lean healthy young women were enrolled into the study. The mean age of controls was 22.8 +/- 4.5 years (range 15-32 years) and their mean body mass index (BMI) was 19.7 +/- 2.6 kg/m(2). Mean blood glucose at 0, 1 and 2 h was 88.2 +/- 7.2, 115.5 +/- 25.5 and 91.8 +/- 20.5 mg/dl, respectively. Corresponding plasma insulin levels were 5.8 +/- 1.1, 32.7 +/- 26.5 and 14.6 +/- 9.6 mIU/l. Peak insulin levels were seen at 1 h and these came down to less than 40% of the peak value by 2 h. Glucose/insulin ratio at 0, 1 and 2 h was 15.6 +/- 3.1, 7.0 +/- 3.1 and 11.4 +/- 7.0. Homeostasis model assessment of insulin resistance (HOMA-IR) was 1.2 +/- 0.2. The age of the PCOS women ranged from 15 to 40 years (mean 23.4 +/- 6.2 years) and their BMI ranged from 16.4 to 50.4 kg/m(2) (mean 27.7 +/- 6.3 kg/m(2)). One hundred and seventy-six (62%) PCOS patients had normal glucose tolerance (NGT), 39 (14%) had impaired fasting glucose (IFG), 49 (17%) had impaired glucose tolerance (IGT) and 21 (7%) had type 2 diabetes mellitus (T2DM). Insulin response was higher in women with PCOS. Peak insulin was observed at 1 h. The difference between 1-h and 2-h post-glucose insulin decreased with worsening glucose tolerance. Both plasma insulin and BMI showed a rising trend from NGT to IFG to IGT. There was no further increase in either insulin or BMI from IGT to T2DM. Glucose/insulin ratio at 0, 1 and 2 h was lower (8.3 +/- 4.2, 2.0 +/- 1.6 and 3.2 +/- 3.5) than that of healthy controls. HOMA-IR was 3.1 +/- 3.0. CONCLUSION: Women with PCOS had an exaggerated insulin response to glucose. Thirty-eight percent of PCOS women had some form of abnormal glucose tolerance. Greater insulin response was seen with impairment of glucose tolerance. Obesity had no effect on fasting insulin or insulin response to oral glucose in PCOS women with NGT.