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Biomedical subjects

R R Henry

Publications and source records attributed to R R Henry.

At least 37 records · Page 2Linked to original sources
PubMed1999

Inhibition of LDL oxidation in vitro but not ex vivo by troglitazone.

Diabetic subjects are at increased risk for developing coronary artery disease, in part because of increased oxidation of LDL, which promotes atherogenesis. Troglitazone, a new antidiabetic drug of the thiazolidinedione class, acts as an insulin sensitizer and improves hyperglycemia. Structurally, it contains a tocopherol moiety similar to vitamin E and has been shown to have antioxidant properties in vitro. Therefore, we evaluated whether troglitazone inhibited LDL oxidation both in vitro and in type 2 diabetic subjects ex vivo. Troglitazone inhibited oxidation of LDL induced by Cu2+ or 2'2'-azobis-2-amidinopropane hydrochloride (AAPH) with 50% inhibition at 1 micromol/l and 100% inhibition at 5-10 micromol/l troglitazone. The inhibition of LDL oxidation by troglitazone also was time dependent. In addition, troglitazone inhibited oxidation of 125I-labeled LDL and its subsequent uptake and degradation by macrophages. To determine whether troglitazone was incorporated into LDL particles or acted in the aqueous milieu, troglitazone was incubated overnight at 37 degrees C with LDL or plasma before LDL re-isolation. After re-isolation, LDL that was incubated with troglitazone was no longer protected from oxidation, compared with probucol-treated LDL, which remained protected. Further, [14C]troglitazone did not get incorporated into LDL. This suggests that troglitazone exerts its antioxidant effect in the aqueous milieu of LDL. Consistent with this was the observation that the lag phases of copper-induced conjugated diene formation, a measure of the susceptibility in vivo, was similar for subjects taking troglitazone (76 +/- 5 min, n = 9) to subjects not taking the drug (77 +/- 3 min, n = 11; NS). Thus, troglitazone may be of value as an aqueous-phase antioxidant in addition to its effect on glucose homeostasis.

Antioxidants↗
PubMed1999

Insulin aspart (B28 asp-insulin): a fast-acting analog of human insulin: absorption kinetics and action profile compared with regular human insulin in healthy nondiabetic subjects.

OBJECTIVE: To study the pharmacokinetic and pharmacodynamic profile of insulin aspart (a new fast-acting human insulin analog) after subcutaneous administration in the deltoid, abdominal, and thigh sites and to compare this profile with regular human insulin (Novolin; Novo Nordisk A/S, Copenhagen). RESEARCH DESIGN AND METHODS: A total of 20 healthy subjects were studied in a single-center six-period double-blind randomized crossover trial with 6 study days and a washout period of 1 week between each single daily dose of the trial drug. Subjects were randomized to receive a single dose of 0.2 U/kg of insulin aspart or regular insulin on each of the 6 study days in three different sites (the deltoid, the abdomen, and the thigh) during a 10-h euglycemic clamp (two drugs and three injection sites). Pharmacokinetic and pharmacodynamic measurements were derived from blood sample measurements of glucose, insulin, and C-peptide during these clamps. RESULTS: The pharmacodynamic data from the euglycemic clamp study showed that, regardless of injection site, the maximal glucose infusion rate (GIR Cmax) was greater and occurred at an earlier time (GIR Tmax) after administration of insulin aspart than regular insulin (GIR Cmax: abdomen 813 vs. 708, deltoid 861 vs. 736, and thigh 857 vs. 720 g/min, P < 0.05 for all; GIR Tmax: abdomen 94 vs. 173, deltoid 111 vs. 192, and thigh 145 vs. 193 g/min, P < 0.05 for all). Pharmacokinetic parameters were also consistent with faster absorption and higher peak insulin concentrations after insulin aspart administration. From all sites, the peak insulin concentration (Cmax) was higher and occurred earlier (Tmax) after administration of insulin aspart than of regular insulin (Cmax: abdomen 501 vs. 260, deltoid 506 vs. 252, thigh 422 vs. 220 pmol/l, P < 0.001 for all sites; Tmax: abdomen 52 vs. 109, deltoid 54 vs. 98, and thigh 60 vs. 107 min, P < 0.01 for all sites). The absorption and glucose-lowering action of insulin aspart did not differ between sites (similar GIR Cmax, Tmax, and area under the curve parameters). However, the duration of the glucose-lowering effect was up to 34 min shorter (P < 0.01) for the abdomen injections than for the deltoid or thigh injections (lower time of 50% glucose disposal). In addition, the amount of glucose infused was significantly lower by 10-14% in the abdomen than in other sites. CONCLUSIONS: Subcutaneous administration of insulin aspart causes a more rapid and intense maximal effect compared with regular insulin during euglycemic clamp studies in nondiabetic subjects. Abdominal administration of insulin aspart has a shorter duration of glucose-lowering effect compared with administration in the deltoid or thigh.

Absorption↗
PubMed1998

Type 2 diabetes care: the role of insulin-sensitizing agents and practical implications for cardiovascular disease prevention.

Millions of Americans are at risk for cardiovascular morbidity and mortality related to disorders of glucose intolerance--particularly type 2 diabetes and prediabetic conditions, including the insulin resistance, or "cardiovascular dysmetabolic," syndrome. The latter is apparently more intricately associated with macrovascular disease--myocardial infarction, stroke, and peripheral vascular disease. In some situations the risk of cardiovascular disease might be reduced by the prevention of diabetes and also by prevention or treatment of the cardiovascular dysmetabolic syndrome. Studies have shown that intensive glycemic control can delay the development of microvascular complications in type 1, and possibly type 2, diabetes. Several longitudinal observational studies have demonstrated a relationship between glycemic control and the development of cardiovascular disease. Prospective clinical intervention trials to address this issue are underway. Insulin may have a role in atherogenesis, both directly and by promoting development of such risk factors as hypertension and dyslipidemia. Genetic factors and mechanisms promoting or discouraging development of glucose intolerance are also under investigation. Lifestyle changes--dietary and exercise modification, weight loss, and smoking cessation--have been shown to have a positive effect on cardiovascular disease risk. Clinical trials suggest that oral antidiabetic agents--particularly the new noninsulin secretagogues (including troglitazone and metformin, which act on the liver and on skeletal muscle)--may be useful in delaying or preventing development of type 2 diabetes and the cardiovascular dysmetabolic syndrome, as well as in their treatment, when present. Both agents, acting primarily by different mechanisms of action, have also demonstrated potential beneficial effects on serum lipid profiles and other cardiovascular risk factors and may be useful in patients with cardiovascular dysmetabolic syndrome who do not yet meet the criteria for diabetes.

Administration, Oral↗
PubMed1998

Elevated cyclins and cyclin-dependent kinase activity in the rhabdomyosarcoma cell line RD.

An important early event in the differentiation of skeletal muscle cells is exit from the cell cycle, after which full expression of the muscle phenotype occurs. Rhabdomyosarcoma (RMS), a tumor of skeletal muscle origin, expresses a number of muscle-specific proteins, including MyoD; however, these cells fail to arrest or differentiate when cultured in differentiation medium (DM). To determine the basis for the failure of RMS cells to differentiate or arrest, we studied the molecular response of the embryonal RMS cell line, RD, to culture in DM. Under these conditions, the retinoblastoma protein (RB) was primarily in the hyperphosphorylated state. This is in contrast to myoblasts cultured in DM, in which the hypophosphorylated form of RB is exclusively present. Measurements of the expression and activities of cyclin-dependent kinases (cdks) cdk2 and cdk4 indicated that RD cells maintained higher levels than do myoblasts, and the activity and abundance of these proteins did not significantly decrease upon culture in DM in RD cells, as they did in myoblasts. Similarly, elevated expression of cyclins D1, E, and A was observed in RD cells. Interestingly, cdk inhibitors are expressed in RD cells, with p16ink4 expression markedly elevated relative to myoblasts. Ectopic expression of p21cip1, p16ink4, or p27kip1 caused a growth arrest of RD cells but not detectable expression of a myogenic marker. Furthermore, a constitutively active RB protein could also inhibit the growth of RD cells without inducing myogenic differentiation. Taken together, these data suggest that the elevated levels of cdk2 and/or cdk4 observed in RD cells contribute to the inability of RD cells to growth arrest when cultured in DM but that these activities alone are not responsible for the failure of RD cells to differentiate.

Cell Cycle↗
PubMed1998

Plasma homocysteine concentrations are regulated by acute hyperinsulinemia in nondiabetic but not type 2 diabetic subjects.

An association between hyperhomocysteinemia and premature atherosclerosis in patients with non-insulin-dependent diabetes mellitus (NIDDM) has recently been described. Little is known about the role of insulin in homocysteine [H(e)] metabolism. We measured plasma H(e) concentrations in the fasting state and during a hyperinsulinemic-euglycemic clamp in normal subjects and patients with NIDDM. Plasma H(e) decreased significantly from 7.2 +/- 2.6 to 6.0 +/- 2.7 mmol/L (P < .01) in normal subjects, but did not change in patients with NIDDM (6.0 +/- 2.7 to 5.9 +/- 2.5 mmol/L, respectively). These data suggest that plasma H(e) concentrations are regulated by acute hyperinsulinemia in normal subjects, but not in insulin-resistant NIDDM subjects. These abnormalities may have implications for the pathogenesis of premature vascular disease associated with NIDDM.

Acute Disease↗
PubMed1998

Effects of tumor necrosis factor-alpha on glucose metabolism in cultured human muscle cells from nondiabetic and type 2 diabetic subjects.

The effects of tumor necrosis factor-alpha (TNF alpha) on glucose uptake and glycogen synthase (GS) activity were studied in human skeletal muscle cell cultures from nondiabetic and type 2 diabetic subjects. In nondiabetic muscle cells, acute (90-min) exposure to TNF alpha (5 ng/ml) stimulated glucose uptake (73 +/- 14% increase) to a greater extent than insulin (37 +/- 4%; P < 0.02). The acute uptake response to TNF alpha in diabetic cells (51 +/- 6% increase) was also greater than that to insulin (31 +/- 3%; P < 0.05). Prolonged (24-h) exposure of nondiabetic muscle cells to TNF alpha resulted in a further stimulation of uptake (152 +/- 31%; P < 0.05), whereas the increase in cells from type 2 diabetics was not significant compared with that in cells receiving acute treatment. After TNF alpha treatment, the level of glucose transporter-1 protein was elevated in nondiabetic (4.6-fold increase) and type 2 (1.7-fold) cells. Acute TNF alpha treatment had no effect on the fractional velocity of GS in either nondiabetic or type 2 cells. Prolonged exposure reduced the GS fractional velocity in both nondiabetic and diabetic cells. In summary, both acute and prolonged treatment with TNF alpha up-regulate glucose uptake activity in cultured human muscle cells, but reduce GS activity. Increased skeletal muscle glucose uptake in conditions of TNF alpha excess may serve as a compensatory mechanism in the insulin resistance of type 2 diabetes.

Adult↗
PubMed1998

Lack of effect of leptin on glucose transport, lipoprotein lipase, and insulin action in adipose and muscle cells.

The effect of leptin on glucose transport, lipogenesis, and lipoprotein lipase activity was studied in cultured rat adipocytes and 3T3-L1 adipocytes. Leptin had no effect on basal and insulin stimulated glucose transport in isolated adipocytes from the rat and the genetically obese mouse. The incorporation of glucose into lipids was also unaffected. Lipoprotein lipase (LPL) activity remained unchanged in response to leptin in these cells, as well as in minced adipose tissue. Leptin also had no effect on both basal and insulin-stimulated glucose transport in cultured rat and human skeletal muscle cells. These studies showed that leptin had no effect on glucose transport, lipoprotein lipase activity, and insulin action in fat and muscle cells in vitro.

3T3 Cells↗
PubMed1998

Troglitazone regulation of glucose metabolism in human skeletal muscle cultures from obese type II diabetic subjects.

To determine the effects of troglitazone on abnormal skeletal muscle glucose metabolism, muscle cultures from type II diabetic patients were grown for 4-6 weeks and then fused for 4 days either without or with troglitazone (1-5 micrograms/mL; chronic studies) or had troglitazone added for 90 min (1-5 micrograms/mL) at completion of fusion (acute studies). Acute troglitazone treatment stimulated glucose uptake, but not glycogen synthase (GS) activity 2-fold (P < 0.05) in a dose-dependent fashion and to the same extent as the addition of maximal (33 nmol/L) insulin. Maximal chronic troglitazone (5 micrograms/mL for 4 days) increased both glucose uptake (from 9.0 +/- 1.5 to 40.9 +/- 8.1 pmol/mg protein.min; P < 0.05) and GS fractional velocity (from 5.4 +/- 0.7% to 20.6 +/- 6.3%; P < 0.05) by approximately 4-fold. At each concentration of chronic troglitazone, glucose uptake rates were similar in the absence and presence of maximal (33 nmol/L) insulin concentrations. In contrast, insulin-stimulated GS activity was greater (P < 0.05) when maximal chronic troglitazone and acute insulin were combined than when chronic troglitazone alone was used. After 4 days of troglitazone, GLUT1 messenger ribonucleic acid and protein increased about 2-fold (P < 0.05) without a change in GLUT4 or GS messenger ribonucleic acid and protein. We conclude that troglitazone has both acute and chronic effects to improve skeletal muscle glucose metabolism of obese type II diabetic subjects. These effects involve direct insulin mimetic stimulatory actions as well as indirect insulin-sensitizing properties.

Adult↗
PubMed1998

Troglitazone effects on gene expression in human skeletal muscle of type II diabetes involve up-regulation of peroxisome proliferator-activated receptor-gamma.

Troglitazone, besides improving insulin action in insulin-resistant subjects, is also a specific ligand for the nuclear receptor peroxisome proliferator-activated receptor-gamma (PPARgamma). To determine whether troglitazone might enhance insulin action by stimulation of PPARgamma gene expression in muscle, total PPARgamma messenger RNA (mRNA), and protein were determined in skeletal muscle cultures from nondiabetic control and type II diabetic subjects before and after treatment of cultures with troglitazone (4 days +/- troglitazone, 11.5 microM). Troglitazone treatment increased PPARgamma mRNA levels up to 3-fold in muscle cultures from type II diabetics (277 +/- 63 to 630 +/- 100 x 10(3) copies/microg total RNA, P = 0.003) and in nondiabetic control subjects (200 +/- 42 to 490 +/- 81, P = 0.003). PPARgamma protein levels in both diabetic (4.7 +/- 1.6 to 13.6 +/- 3.0 AU/10 microg protein, P < 0.02) and nondiabetic cells (7.4 +/- 1.0 to 12.7 +/- 1.8, P < 0.05) were also upregulated by troglitazone treatment. Increased PPARgamma was associated with stimulation of human adipocyte lipid binding protein (ALBP) and muscle fatty acid binding protein (mFABP) mRNA, without change in the mRNA for glycerol-3-phosphate dehydrogenase, PPARdelta, myogenin, uncoupling protein-2, or sarcomeric alpha-actin protein. In summary, we showed that troglitazone markedly induces PPARgamma, ALBP, and mFABP mRNA abundance in muscle cultures from both nondiabetic and type II diabetic subjects. Increased expression of PPARgamma protein and other genes involved in glucose and lipid metabolism in skeletal muscle may account, in part, for the insulin sensitizing effects of troglitazone in type II diabetes.

Adult↗
PubMed1998

The Veterans Affairs Implantable Insulin Pump Study: effect on cardiovascular risk factors.

OBJECTIVE: To determine whether implantable insulin pump (IIP) and multiple-dose insulin (MDI) therapy have different effects on cardiovascular risk factors in insulin-requiring patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: A randomized clinical trial was conducted at seven Veterans Affairs medical centers in 121 male patients with type 2 diabetes between the ages of 40 and 69 years receiving at least one injection of insulin per day and with HbA1c, levels of > or =8% at baseline. Weights, blood pressures, insulin use, and glucose monitoring data were obtained at each visit. Lipid levels were obtained at 0, 4, 8, and 12 months, and free and total insulin levels were obtained at 0, 6, and 12 months. All medications being taken were recorded at each visit. RESULTS: No difference in absolute blood pressure, neither systolic nor diastolic, was seen between patients receiving MDI or IIP therapy, but significantly more MDI patients required anti-hypertensive medications. When blood pressure was modeled against weight and time, IIP therapy was significantly better than MDI therapy for systolic blood pressure in patients with BMI <33 and for diastolic blood pressure in patients with BMI >34 kg/m2. Total cholesterol levels decreased in the overall sample, but IIP patients exhibited significantly higher levels than MDI patients. Triglyceride levels increased over time for both groups, with IIP patients having significantly higher levels than patients in the MDI group. BMI was a significant predictor of, and inversely proportional to, HDL cholesterol level. No difference in lipid-lowering drug therapy was seen between the two groups. Free insulin and insulin antibodies tended to decrease in the IIP group as compared with the MDI group. C-peptide levels decreased in both groups. CONCLUSIONS: IIP therapy in insulin-requiring patients with type 2 diabetes has advantages over MDI therapy in decreasing the requirement for antihypertensive therapy and for decreasing total and free insulin and insulin antibodies. Both therapies reduce total cholesterol and C-peptide levels.

Adult↗
PubMed1997

Thiazolidinediones.

The thiazolidinediones are a unique class of compounds that exert direct effects on the mechanisms of insulin resistance and result in improved insulin action and reduced hyperinsulinemia. Troglitazone is the first of these compounds to be approved for use in humans and has the potential not only to reduce glycemia and insulin requirements in type II diabetes but to improve other components of the insulin resistance syndrome including dyslipidemia, hypertension, and accelerated cardiovascular disease. Such compounds also hold promise for the prevention of type II diabetes and for the treatment of other insulin-resistant states including polycystic ovary disease. In addition to the novel mechanism of action through binding and activation of PPARs, troglitazone has other unique advantages, including once-a-day administration, a low incidence of minor side effects, no known drug interactions, hepatic metabolism and secretion, and potent antioxidant properties. Thiazolidinedione compounds such as troglitazone provide an important additional resource for the health care provider in the management of type II diabetes and other components of the insulin resistance syndrome.

Diabetes Mellitus, Type 2↗
PubMed1997

Effects of multiple daily insulin injections and intraperitoneal insulin therapy on cholesteryl ester transfer and lipoprotein lipase activities in NIDDM.

Although the relationship between the actions of cholesteryl ester transfer protein (CETP) and atherosclerosis is complex, a strong body of evidence suggests that its activity (cholesteryl ester transfer [CET]) is proatherogenic. We have previously shown that CET is increased in IDDM patients receiving conventional subcutaneous insulin treatment and normalized when systemic insulin levels are lowered with intraperitoneal insulin delivery (IP). Since CET has been found by many observers to also be accelerated in NIDDM, we sought to determine whether the same salutary effect could be achieved in insulin-requiring NIDDM men before and 7 months after randomization to an intensive treatment regimen (Rx) of either IP (n = 9) or multiple daily insulin injections (MDI; n = 13). HbA1c improved to the same degree in both groups (MDI group: 9.4 +/- 1.1% pre-Rx vs. 7.2 +/- 0.7% post-Rx [P < 0.001]; IP group: 9.2 +/- 1.3% pre-Rx vs. 7.1 +/- 0.5% post-Rx [P < 0.001]). Compared with pre-Rx levels, plasma triglycerides were not significantly changed by either treatment (MDI group: 136 +/- 80 mg/dl pre-Rx vs. 139 +/- 87 mg/dl post-Rx; IP group: 157 +/- 63 mg/dl pre-Rx vs. 188 +/- 89 mg/dl post-Rx), though an upward trend followed IP. Before randomization, CET estimated with both mass and isotopic assays was greater in the NIDDM subjects than in nondiabetic control subjects (P < 0.001). With improved glycemic control, CE mass transfer declined in both groups, but only reached normal levels in the IP group (MDI group at 2 h: 49.0 +/- 13.7 [mean +/- SD] pg pre-Rx vs. 29.5 +/- 15.3 microg post-Rx [-39.7%, P < 0.01]; IP group at 2 h: 40.8 +/- 23.3 microg pre-Rx vs. 10.9 +/- 6.5 microg post-Rx [-73.2%, P < 0.05]) and remained abnormally increased (P < 0.005) in the subjects receiving MDI. Total lipolytic activity after intensive treatment was unchanged from pretreatment levels, which were similar to those of the reference group. Although directional changes in lipoprotein lipase (LpL) and hepatic triglyceride lipase (HTGL) similar to those found in IDDM after MDI and IP were observed, they were not statistically significant. Thus, while improved glycemic control alone achieved by either MDI or IP reduced the pathological increase in CET in these insulin-treated NIDDM men, normalization was only achieved in those treated with IP. Despite near-normal HbA1c levels, CET remained abnormally increased in NIDDM patients treated rigorously with conventional subcutaneous insulin delivery.

Adult↗
PubMed1997

Regulation of glycogen synthase activity in cultured skeletal muscle cells from subjects with type II diabetes: role of chronic hyperinsulinemia and hyperglycemia.

Human skeletal muscle cultures (HSMCs) from type II diabetic subjects were used to determine whether metabolic abnormalities such as hyperglycemia or hyperinsulinemia contribute to the defective muscle glycogen synthase (GS) activity present in this disorder. Following approximately 6 weeks of growth, diabetic cultures were fused for 4 days in normal, hyperglycemia, or hyperinsulinemia medium. Fusion of diabetic HSMCs in hyperglycemia medium (20 mmol/l vs. 5.5 mmol/l) had no effect on GS fractional velocity (FV) or mRNA levels, but impaired acute insulin-stimulation of glycogen synthesis and GS activity at 0.1 mmol/l glucose-6-phosphate, and reduced GS protein content by approximately 15% (P < 0.05). Fusion of diabetic muscle cultures in hyperinsulinemia medium (30 micromol/l vs. 22 pmol/l) improved basal GS activity, increasing the reduced GS FV by approximately 50% (P < 0.05), and decreasing the elevated Km(0.1) (half-maximal substrate concentration) by approximately 47% (P < 0.05). Hyperinsulinemia also significantly increased (P < 0.05) the reduced GS mRNA and protein levels of diabetic muscle to levels similar to that in nondiabetic subjects. In contrast to the improvements in the basal state, hyperinsulinemia completely abolished acute insulin responsiveness of GS activity and glycogen synthesis in muscle of type II diabetic subjects. The combination of hyperinsulinemia and hyperglycemia produced effects on both basal and insulin-responsive GS FV and mRNA similar to hyperinsulinemia alone, but hyperinsulinemia prevented hyperglycemia's effect of lowering GS protein and glycogen synthesis. We concluded that, in diabetic muscle, hyperinsulinemia may serve to partially compensate for the impaired basal GS activity and for the adverse effects of hyperglycemia on GS protein content, activity, and glycogen formation by both pre- and posttranslational mechanisms. Despite these beneficial effects, hyperinsulinemia also induces severe impairment of insulin-stimulated GS activity and glycogen formation, which may contribute to acquired muscle insulin resistance of type II diabetes.

Adult↗
PubMed1997

PPAR-gamma gene expression is elevated in skeletal muscle of obese and type II diabetic subjects.

The peroxisome proliferator activated receptor PPAR-gamma has been identified as a nuclear receptor for thiazolidenediones, which are compounds with insulin-sensitizing properties in several tissues, including skeletal muscle. To determine whether this receptor is expressed and possibly involved in insulin action/resistance in skeletal muscle, PPAR-gamma mRNA abundance and its regulation by insulin were quantified in muscle tissue and cultures from lean and obese nondiabetic and type II diabetic subjects using competitive reverse transcription-polymerase chain reaction (RT-PCR). In muscle biopsy specimens, PPAR-gamma mRNA was elevated in obese nondiabetic and type II diabetic subjects (23.4 +/- 4.2 and 28.0 +/- 5.69 x 10(3) copies/microg total RNA, respectively; both P < 0.05) compared with lean nondiabetic control subjects (9.4 +/- 2.3 x 10(3) copies/microg total RNA). Significant positive correlations were present among skeletal muscle PPAR-gamma mRNA levels, BMI (r = 0.67, P < 0.01), and fasting insulin concentration (r = 0.76, P < 0.001). PPAR-gamma mRNA levels were also elevated in muscle cultures from type II diabetic subjects compared with lean nondiabetic control subjects (330.1 +/- 52.9 vs. 192.1 +/- 27.0 x 10(3) copies/microg total RNA, P < 0.05). Insulin stimulation of muscle tissue (by hyperinsulinemic-euglycemic clamp for 3-4 h) or muscle cultures (30 nmol/l for 120 min) stimulated PPAR-gamma mRNA expression up to fourfold (10.0 +/- 2.7 to 41.3 +/- 7.4 x 10(3) copies/microg total RNA, P < 0.05, and 174.9 +/- 56.9 to 268.2 +/- 78.6 x 10(3) copies/microg total RNA, P < 0.05, respectively). In summary, PPAR-gamma mRNA expression in human skeletal muscle is acutely regulated by insulin and is increased in both obese nondiabetic and type II diabetic subjects in direct relation to BMI and fasting insulinemia. We conclude that abnormalities of PPAR-gamma may be involved in skeletal muscle insulin resistance of obesity and type II diabetes.

Adult↗
PubMed1997

Strategies for preventing type II diabetes. What can be done to stem the epidemic?

Non-insulin-dependent (type II) diabetes is a major target for prevention because of its staggering emotional and financial burdens on society. The theory behind preventive efforts is that individuals at high risk often show signs of impaired glucose tolerance before diabetes fully develops. Once identified, these patients may respond to several pharmacologic and nonpharmacologic interventions that lower blood glucose levels and improve cardiovascular fitness with few adverse effects. However, the long-term efficacy of these approaches is uncertain. Information from the National Institutes of Health Diabetes Prevention Program should help clarify the impact of preventive measures and their cost-effectiveness.

Diabetes Mellitus, Type 2↗
PubMed1997

Risk and resilience in the cognitive functioning of children born to HIV-1-infected mothers: a preliminary report.

Although biologic and environmental risk factors show an age-dependent effect on children's cognitive development, outcome studies have yet to consider the role such factors play in the development of children born to HIV-1-infected women. This study explored the age-dependent differential impact of such risk factors on the cognitive functioning of children exposed in utero to HIV-1. Eighty-two children were administered a standardized measure of cognitive functioning and divided into two groups depending on their age when tested. Group 1 included children age 2 to 29 months (n = 46); Group 2 included children age 30 to 101 months (n = 36). Correlations between cognitive test scores and specific risk factors revealed an age-related double-dissociation. Serostatus and percent of CD4 cells correlated moderately with cognitive test scores in Group 1; however, these correlations were attenuated and nonsignificant in Group 2. Conversely, caregiver status and cognitive test scores were uncorrelated in Group 1, but were correlated in Group 2. These findings support a risk and resilience model of development. That is, in the context of biologic risk factors, aspects of the child's environment may either facilitate or hinder cognitive development.

AIDS Dementia Complex↗