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Biomedical subjects

J Krakoff

Publications and source records attributed to J Krakoff.

9 recordsLinked to original sources
PubMed2006

Comparison of plasma insulin levels after a mixed-meal challenge in children with and without intrauterine exposure to diabetes.

BACKGROUND: The diabetic intrauterine environment is a known risk factor for the development of diabetes in the offspring. OBJECTIVE: We compared anthropometric and metabolic characteristics of 41 nondiabetic children whose mothers developed diabetes either before (ODM, n = 19, 9.3 +/- 1.1 yr) or after (OPDM, n = 22, 9.5 +/- 1.3 yr) the pregnancy of interest. Maternal diabetes status was established from OGTT results before, during, and after the pregnancy of interest. DESIGN: After consuming a standardized diet for 2 d, a mixed-meal breakfast was given after an overnight fast. Fasting concentrations and responses of plasma glucose and insulin were evaluated using linear regression analyses to assess potential independent determinants of plasma insulin concentration at each time point. RESULTS: After adjustment for age and sex, there were no differences between ODM and OPDM children for maternal age at diagnosis, height, weight, body mass index, BMI z score, or percent body fat (dual energy x-ray absorptiometry). After adjusting for age, sex, percent body fat, and the corresponding glucose level at each time point, ODM had a lower plasma insulin level at the 15-min time point during the meal test than OPDM (P = 0.01). CONCLUSION: A lower initial insulin response to a standard mixed-meal challenge can be detected in nondiabetic ODM compared with OPDM children as early as 9 yr of age. This response may be another indicator for an attenuated early insulin response and explain the increased risk for diabetes in these children.

Adult↗
PubMed2006

Increasing incidence of proteinuria and declining incidence of end-stage renal disease in diabetic Pima Indians.

The introduction of more efficacious treatments for diabetic kidney disease may slow its progression, but evidence for their effectiveness in populations is sparse. We examined trends in the incidence of clinical proteinuria, defined as a urinary protein-to-creatinine ratio >0.5 g/g, and diabetic end-stage renal disease (ESRD), defined as death from diabetic nephropathy or onset of dialysis, in Pima Indians with type 2 diabetes between 1967 and 2002. The study included 2189 diabetic subjects >/=25 years old. During follow-up, 366 incident cases of proteinuria occurred in the subset of 1715 subjects without proteinuria at baseline. The age-sex-adjusted incidence rate of proteinuria increased from 24.3 cases/1000 person-years (pyrs) (95% confidence interval (CI) 18.7-30.0) in 1967-1978 to 35.4 cases/1000 pyrs (95% CI 28.1-42.8) in 1979-1990 and 38.9 cases/1000 pyrs (95% CI 31.2-46.5) in 1991-2002 (P(trend)<0.0002). In each period, the age-sex-adjusted incidence of proteinuria increased with diabetes duration, but diabetes duration-specific incidence was stable throughout the study period (P=0.8). The age-sex-adjusted incidence of ESRD increased between 1967 and 1990 and declined thereafter. The incidence of proteinuria increased over 36 years in Pima Indians as the proportion of people with diabetes of long duration increased. On the other hand, the incidence of ESRD declined after 1990, coinciding with improved control of blood pressure, hyperglycemia, and perhaps other risk factors.

Adult↗
PubMed2001

Use of a parenteral propylene glycol-containing etomidate preparation for the long-term management of ectopic Cushing's syndrome.

Chronic severe hypercortisolism is associated with life-threatening infections, diabetes and a high surgical mortality rate. Oral medical therapy can inhibit steroidogenesis and reduce the risk of these complications. However, apart from a few reports using an ethyl alcohol formulation of the iv anesthetic etomidate, there is no well-tested parenteral steroidogenesis inhibitor. We used the propylene glycol preparation of etomidate available in the United States to control hypercortisolism in a 39-yr-old man with ectopic ACTH secretion who was unable to take oral medications. Etomidate was administered over a period of 5.5 months. We titrated the dose of etomidate daily using serum cortisol levels, to avoid steroid over replacement and allow for a response to ongoing stress. A reduced dose during a period of acute renal failure achieved adequate control of hypercortisolemia. Suppression of steroidogenesis persisted for at least 14 d and perhaps as long as 6 wk after cessation of the medication. Except for transient myoclonus, the patient tolerated this preparation well. Parenteral propylene glycol containing etomidate can be used safely for a prolonged period to reduce hypercortisolemia in patients unable to take oral medications.

Acute Kidney Injury↗
PubMed2001

Gamma globulin levels predict type 2 diabetes in the Pima Indian population.

It has been proposed that inflammation or infection may contribute to the development of type 2 diabetes. We examined whether serum gamma globulin, a nonspecific measure of the humoral immune system, predicted changes in glucose tolerance in 2,530 members of the Pima Indian population, a group with a marked predisposition to type 2 diabetes. Cross-sectionally, gamma globulin was positively related to age (r = 0.08, P < 0.0005), BMI (r = 0.09; P < 0.0001), and female sex (P < 0.0001). Gamma globulin concentrations were familial, being positively correlated among siblings (r = 0.23; P < 0.0001) and between parents and their children (mother/child: r = 0.17, P < 0.0001; father/child: r = 0.25, P < 0.0001). Gamma globulin concentrations were higher with greater degrees of American Indian heritage (P < 0.004, with adjustment for age, sex, and BMI) and in the presence of a family history of type 2 diabetes (P < 0.04). Higher gamma globulin levels predicted risk of diabetes. In univariate analysis, a 1 SD difference in gamma globulin was associated with a 20% higher incidence of diabetes in those who were normal glucose tolerant at baseline (hazard rate ratio 1.20 [CI 1.11-1.30]; P < 0.0001) and remained as a significant predictor of diabetes, even when controlled for effects of sex, BMI, and 2-h glucose as additional predictors (hazard rate ratio for 1 SD difference in gamma globulin, 1.14 [1.05-1.24]; P = 0.002). Gamma globulin was also associated in univariate analysis with later development of impaired glucose tolerance (IGT) (hazard rate ratio 1.15 [1.07-1.23]; P < 0.0001), but not with the transition from IGT to diabetes (hazard rate ratio 1.04 [0.90-1.20]; P = 0.6). Thus, gamma globulin levels predict increased risk of diabetes in the Pima population. We suggest that immune function or activation may play a role in the development of type 2 diabetes.

Adult↗
PubMed2001

Comparison of the effect of plasma glucose concentrations on microvascular disease between Pima Indian youths and adults.

OBJECTIVE: To examine whether the current adult guidelines for diagnosis of diabetes are applicable to youth (age <20 years). RESEARCH DESIGN AND METHODS: We analyzed fasting plasma glucose (FPG) and 2-h plasma glucose (PG) in two groups of Pima Indians, youths aged 5-19 years and adults aged 20-34 years, in relation to the incidence of microvascular disease when subjects were reexamined at ages 25-39 (youths) and 40-54 (adults). Microvascular disease was defined as retinopathy or a urine protein-to-creatinine ratio > or =0.5 g. RESULTS: An increase in the incidence of microvascular disease occurred at nearly the same level of glycemia in both groups. For youths, this increase occurred at FPG approximately 7.3 mmol/l and 2-h PG approximately 10.0 mmol/l; for adults, this increase occurred at FPG approximately 7.5 mmol/l and 2-h PG approximately 10.3 mmol/l. Sensitivity of the adult diagnostic guidelines of FPG > or =7.0 mmol/l and 2-h PG > or =11.1 mmol/l for the detection of microvascular disease was much lower (with higher specificity) in youths than in adults. Receiver operating characteristics (ROC) curve areas were lower for FPG and 2-h PG for youths, suggesting that microvascular disease was less strongly predicted by baseline glucose. CONCLUSION: The current adult guidelines for diagnosis of diabetes are applicable to youth, as they identify a population at high risk of microvascular complications.

Adolescent↗
PubMed2000

The role of fibric acid derivatives in the secondary prevention of coronary heart disease.

Fibric acid derivatives effectively lower triglycerides and raise high-density lipoprotein (HDL) cholesterol, but their effect on low-density lipoprotein (LDL) cholesterol is weakly beneficial (small decreases) to adverse (small increases) and varies according to the triglyceride level. Early primary prevention studies of atherosclerosis using the fibric acid derivative clofibrate showed only modest effects on atherosclerosis and an alarming increase in mortality in the intervention group. Although the Helsinki Heart Study later demonstrated that gemfibrozil decreased cardiac endpoints in primary prevention without increasing total mortality, the efficacy of fibric acid derivatives in both primary and secondary prevention of atherosclerosis has remained widely in doubt. Nevertheless, many patients with atherosclerosis have normal or even low LDL cholesterol, but elevated triglyceride, and low HDL cholesterol; furthermore, even aggressive LDL cholesterol lowering with HMG Co-A (3-hydroxy 3-methylglutaryl coenzyme A) reductase inhibitors (statins) fails to prevent the majority of atherosclerotic events. These findings have kindled increased interest in the use of fibric acid derivatives in atherosclerosis prevention, especially through treatment of non-LDL dyslipidemias. Recent studies with angiographic and clinical end-points have now provided evidence for a beneficial effect of at least some drugs in this class in the secondary prevention of atherosclerosis.

Bezafibrate↗
PubMed1997

Ketoacidosis in Apache Indians with non-insulin-dependent diabetes mellitus.

BACKGROUND: Although more classically associated with insulin-dependent diabetes mellitus, diabetic ketoacidosis (DKA) can occur in some patients with non-insulin-dependent diabetes mellitus (NIDDM). To better define the clinical features that may be associated with ketoacidosis in patients with NIDDM, we reviewed the medical histories of Apache Indians with NIDDM who had been treated for an episode of DKA. METHODS: Cases of ketoacidosis among patients with NIDDM were identified at 2 separate Apache Indian reservations. Chart data were used to confirm and characterize the diagnosis of NIDDM, the metabolic disturbances associated with DKA, and the historical features of the patients. RESULTS: Among 724 patients with NIDDM, 17 patients experiencing at least 1 episode of DKA were identified. The mean (+/-SD) age at the time of the episode was 40.8 +/- 13.9 years. The patients were predominantly male (15[88%]), with a mean (+/-SD) body mass index (calculated as the weight in kilograms divided by the square of the height in meters) of 24.9 +/- 4.4 kg/m2. Causes of DKA included infections (8[47%]) and omission of treatment (3/15[20%]). Concurrent abuse of alcohol was noted in 4 (27%) of the patients. In addition, a lifetime history of alcohol abuse was noted in 15 (94%) of 16 patients. CONCLUSIONS: This report confirms the growing recognition that DKA occurs in some patients with NIDDM. The present study also adds male sex, alcohol abuse, and relatively low body mass index as clinical factors that may play a role in the development of DKA in this setting.

Adult↗