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PubMed2005

Diabesity: are weight loss medications effective?

Weight reduction has been shown to improve glycemic control and cardiovascular risk factors associated with insulin resistance in obese individuals with type 2 diabetes mellitus. Therapeutic options for these patients include promoting weight loss (non-pharmacologic and pharmacologic treatment) and improving glycemic control, as well as treating common associated risk factors such as arterial hypertension and dyslipidemias. This article provides an overview of anti-obesity drugs used in the treatment of obese individuals with type 2 diabetes. The most widely investigated drugs, sibutramine and orlistat, result in modest, clinically worthwhile weight loss, with demonstrable improvements in many co-morbidities, among them, type 2 diabetes. Clinical trials with these anti-obesity medications in cohorts of obese diabetic patients have been reviewed as well as cathecolaminergic agents (diethylpropion [amfepramone], fenproporex, mazindol, ephedrine-caffeine combination), serotoninergic drugs (fenfluramine, dexfenfluramine, fluoxetine), and other drugs that have some action on weight loss (the antidiabetic agent metformin, anti-epileptic agents topiramate and zonisamide, and the antidepressive bupropion [amfebutamone]). These trials show variable benefits in terms of effects on glucose profiles.

Anti-Obesity Agents↗

PubMed1997

High normo- or low microalbuminuria: basis for intervention in insulin-dependent diabetes mellitus.

Recent studies have further elucidated the association between blood pressure and albumin excretion in insulin-dependent diabetes mellitus (IDDM) patients with (i) normal urinary albumin excretion (UAE), and (ii) moderate microalbuminuria (20 to 70 micrograms/min). In a study comprising 117 normoalbuminuric (UAE < 20 micrograms/min) patients we performed 24-hour ambulatory blood pressure monitoring (AMBP), and short-term power spectral analysis of RR interval oscillations. In comparison with the group with a UAE below the median, patients with UAE above the median were characterized by: significantly higher 24-hour systolic and diastolic AMBP, significantly reduced short-term RR interval variability, and significantly higher HbA1c. In a double blind study, normotensive IDDM patients with moderate microalbuminuria (20 to 70 micrograms/min) were randomized to either lisinopril (20 mg once a day, N = 12) or placebo (N = 10) for two years. In the lisinopril group there were significant reductions in 24-hour systolic and diastolic AMBP compared to the placebo group. Lisinopril did not attenuate the diurnal blood pressure variation. UAE tended to be reduced in the lisinopril group. A significantly positive association between changes in AMBP and changes in UAE was present in the placebo group in contrast to the lisinopril group. Changes in UAE were strongly and positively associated with changes in filtration fraction in the lisinopril treated group. In conclusion, interactions between albumin excretion, blood pressure, autonomic function, and glycemic status are already detectable within the normoalbuminuric range in IDDM patients. Angiotensin converting enzyme inhibitor (ACEi) treatment in a small group of normotensive IDDM patients with moderate microalbuminuria reduces blood pressure without attenuating diurnal blood pressure variation, tends to reduce albumin excretion, and abolishes the association between changes in UAE and changes in blood pressure observed in the placebo group. ACEi intervention in selected normoalbuminuric high risk patients (high-normal UAE, high-normal blood pressure, and poor glycemic control) would be of interest.

Albuminuria↗

PubMed1988

High spontaneous premature labor rate in insulin-dependent diabetic pregnant women: an association with poor glycemic control and urogenital infection.

The incidence of spontaneously occurring premature labor in insulin-dependent diabetic pregnancies is unclear, because previous studies have been confounded by a high rate of iatrogenic prematurity. The purpose of this study was to determine, in a large population of insulin-dependent diabetic pregnant women, the rate of spontaneous occurrence of premature labor and the various factors that may affect it. We hypothesized a priori that spontaneously occurring premature labor occurs at a high rate in insulin-dependent diabetic pregnant women, mainly because of poor control of diabetes during pregnancy, and is related to the presence of polyhydramnios and hypomagnesemia. One hundred forty-five insulin-dependent diabetic women undergoing 181 pregnancies were recruited since 1978 in an interdisciplinary prospective study. The goals of glucose control were a fasting blood glucose less than 100 mg/dL and a 90-minute postprandial glucose less than 140 mg/dL. The rate of spontaneous premature labor, 31.1%, was significantly higher (P less than .01) than that in a control population managed by the same obstetricians in similar clinical settings (20.2%). The following variables were not significantly associated with the onset of premature labor: maternal age, parity, gravidity, diabetic class according to White, presence of renal disease or retinopathy, previous elective abortion, chronic hypertension or pregnancy-induced hypertension, cigarette smoking, first-trimester or post-20 weeks' gestation vaginal bleeding, maternal serum magnesium concentration, or polyhydramnios.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1999

Day-to-day consistency in amount and source of carbohydrate intake associated with improved blood glucose control in type 1 diabetes.

OBJECTIVE: To determine if a relationship exists between blood glucose control and variability in nutrient intake from day-to-day in subjects with type 1 diabetes. METHODS: Two three-day diet records and one measurement of glycated hemoglobin (HbA1c) were obtained from 272 subjects with type 1 diabetes treated with a mixture of regular and NPH insulins before breakfast and supper and using a standardized algorithm to adjust insulin dose according to the results of self-monitoring of blood glucose two to four times daily. Day-to-day variation in nutrient intake was expressed as the coefficient of variation (CV = SDx100/mean). RESULTS: Nutrient intakes in the study population (mean +/- SD) were energy 8.35+/-2.43 MJ, fat 81+/-30 g, protein 94+/-28 g, carbohydrate 227+/-68 g, starch 126+/-38 g and dietary fiber 20+/-6 g with diet glycemic index being 84.2+/-7.4. Neither energy, nutrient intakes nor insulin dose was significantly related to HbA1c. Day-to-day variation of carbohydrate (p = 0.0097) and starch (p = 0.0016) intakes and diet glycemic index (p = 0.033) was positively related to HbA1c, and the associations remained significant when adjusted for age, sex, duration of diabetes and BMI. Day-to-day variation in energy, protein or fat intakes was not related to HbA1c. CONCLUSIONS: Consistency in the amount and source of carbohydrate intake from day-to-day is associated with improved blood glucose control in people with type 1 diabetes, a result which supports continued educational efforts to achieve adherence to a diabetes diet plan. This conclusion may not apply to people on intensified insulin therapy who adjust their insulin dose based on their actual carbohydrate intake at each meal.

Adolescent↗

PubMed1992

Therapeutic effect of guar gum in patients with non-insulin-dependent diabetes mellitus.

Diets with a high-fiber content have been shown to produce some beneficial effects on metabolic factors in subjects with NIDDM. However, some controversies still exist. In this report, the long-term effect of guar gum (Guarina) on both glycemic and blood lipid profiles was assessed in a randomized, double-blind and cross-over study on 16 (seven male and nine female) subjects with NIDDM. Each subject received placebo (P) and Guarina (G) treatment for two eight-week periods separated by a four-week period to facilitate wash-out. Fasting plasma glucose levels showed significant improvement during G treatment but not during P treatment (151.7 +/- 7.9 vs 168.6 +/- 12.2 mg/dl, p less than 0.01 by paired Student's t test). Hemoglobin Alc levels decreased significantly during G treatment but not during P treatment (6.9 +/- 0.2 vs 7.2 +/- 0.8%, p less than 0.001). Fasting insulin concentrations also showed significant lowering during G treatment but not during P treatment (18.3 +/- 2.1 vs 23.1 +/- 2.9 U/ml, p less than 0.005). Other variables, including serum total cholesterol, triglyceride, HDLc, LDLc, sodium, potassium, chloride, magnesium and calcium levels showed no significant changes during G or P treatment. Ten out of the 16 patients (62.5%) suffered from side effects; these included abdominal cramps (one case), diarrhea (seven cases) and skin itching (one case). In conclusion, guar gum effectively lowers fasting plasma glucose and HbAlc levels in subjects with NIDDM. Hyperinsulinemia could also be ameliorated. The effectiveness and side effects of guar gum treatment should be cautiously evaluated in each NIDDM subject.

Adult↗

PubMed1996

Psychosocial stress and the insulin resistance syndrome.

We examined the association between psychosocial stress-related variables and insulin resistance syndrome (IRS) risk-factor clustering. In 90 middle-aged male volunteers, psychosocial stress-related variables, defined as feelings of excessive tiredness and as personality and behavioral factors reflecting a stress-inducing life-style (type A behavior, hostility, and anger), were significantly correlated with the hyperinsulinemia, hyperglycemia, dyslipidemia, hypertension, increased abdominal obesity, and increased plasminogen activator inhibitor-1 (PAI-1) antigen comprising the IRS. The correlations remained significant after adjusting for body mass index (BMI), age, educational level, smoking status, alcohol consumption, and physical activity. However, the different stress-related factors reflected different risk-factor clustering profiles. Type A behavior was associated with normotension and a normal metabolic profile (canonical r = .50, chi2(36) = 59.1, P = .008). Hostility was related to elevated systolic blood pressure (SBP) and elevated triglycerides (TGs) (canonical r = .38, chi2(14) = 23.2, P = .052), whereas feelings of excessive tiredness were related to abdominal obesity, augmented glycemic responses to glucose ingestion, dyslipidemia, and increased PAI-1 antigen (canonical r = .39, chi2(24) = 36.8, P = .046). Although hostility and feelings of excessive tiredness have partly overlapping but clearly different clinical and metabolic correlates, their combination represents a full-blown IRS. Thus, even though insulin resistance is presumably to some extent genetically determined, these results suggest that considering psychosocial stress may be beneficial in understanding IRS risk-factor clustering.

Adult↗

PubMed1997

Urinary albumin excretion rate and cardiovascular disease in Spaniard type 2 diabetic patients.

To assess the prevalence of urinary albumin excretion abnormalities and their associations with cardiovascular disease or its classical risk factors in type 2 diabetes mellitus, 1348 clinic-proceeding patients have been studied retrospectively. The overnight urinary albumin excretion rate, blood pressure, smoking, ophthalmic and cardiovascular status, current therapies, estimates of glycemic control, plasma lipids, serum creatinine and uric acid have been ascertained. 767 (56.8%) patients were found normoalbuminuric, 461 (34.1%) microalbuminuric and 120 (8.9%) macroalbuminuric. In bivariate analyses, the urinary albumin excretion rate had statistically significant (P < 0.05) relationships with age, duration of diabetes, male sex, waist-to-hip ratio, systolic and diastolic pressure, coronary heart disease, cerebrovascular disease, peripheral vascular disease, hypertension, antihypertensive therapy, laser-treated retinopathy, kind of treatment, smoking habit, fasting glycaemia, HbA1c, creatinine, uric acid, triglycerides, high density lipoprotein (HDL)-cholesterol and apolipoprotein B. Borderline statistically significant (P < 0.1) relationships were found with hypolipidaemic therapy, insulin dose, non-HDL-cholesterol, apolipoprotein A1 and lipoprotein (a). In a multivariate stepwise logistic regression model, HbA1c, hypertension, male sex, age, diastolic blood pressure, coronary heart disease and body-mass index were sequentially selected as variables independently associated with microalbuminuria. Serum creatinine, HbA1c, male sex and hypertension were sequentially selected as independently associated with macroalbuminuria. Micro and macroalbuminuria are frequent abnormalities associated with poorly controlled and complicated disease, with overt cardiovascular disease and its classical risk factors as well as with the male sex.

Aged↗

PubMed2001

Hyperinsulinemia and insulin resistance related metabolic syndrome.

BACKGROUND: A cross-sectional study in northern Taiwan was conducted to investigate the role of serum insulin level on the development of hyperglycemia, hypertension, obesity and hyperlipidemia. METHODS: Demographic data (age, gender), body mass index, blood pressure, and laboratory blood tests (uric acid, total cholesterol, triglycerides, glucose and immunoreactive insulin when fasting and two hours after loading 75 gm glucose) were collected. A logistic model or polychotomous model, treating each chronic disease (hyperglycemia, hypertension, obesity and hyperlipidemia) as a dependent variable, were fitted to study the effect of serum insulin level. RESULTS: Four hundred and twenty one volunteers (women:men = 237:184) were recruited from 1991 to 1993. Women were more obese and had more hyperglycemia, while the frequency of hyperuricemia was lower than of men. Women with a higher level of the sum of fasting and 2-hour post glucose load insulin (SIRI) levels had higher frequencies of glucose intolerance, hypertension, obesity and hyperlipidemia, whereas SIRI was related to only obesity and hyperlipidemia in men. The high plasma SIRI was a risk factor for both impaired glucose tolerance (IGT) and obesity in women. Men with a high plasma SIRI showed a more than three-fold risk of obesity. CONCLUSIONS: We have observed that a higher serum insulin level was significantly associated with the development of metabolic manifestations (glycemic status and obesity) in a suburban community in northern Taiwan. Men and women with a higher serum insulin level probably had a greater chance of developing obesity, and women had a greater chance of developing IGT.

Adolescent↗

PubMed2002

A preliminary evaluation of the efficacy and safety of Cogent db (an ayurvedic drug) in the glycemic control of patients with type 2-diabetes.

OBJECTIVES AND STUDY DESIGN: A nonrandomized, non-placebo-controlled clinical trial to evaluate the efficacy of Cogent db (an herbal preparation; Cybele Herbal Laboratories [PVT] Ltd. Kochi, Kerala State, India) as an adjuvant in the treatment of patients with type 2 diabetes was carried out during a 3-month period. SETTINGS/LOCATION: This study was conducted in two major peripheral clinics of Kuala Lumpur in the Klang Valley, Malaysia. SUBJECTS: A total of 39 Cogent db-treated cases and 40 age-matched controls were recruited for this preliminary study. Nineteen (19) subjects (10 and 9 from control and treatment groups, respectively) dropped out of the study leaving a total of 60 subjects (30 each for control and treatment groups) who completed the study. INTERVENTIONS: All subjects in the treatment group were given Cogent db (2 tablets three times daily after each meal) in addition to the regular allopathic drugs (Daonil, [Aventis Farma, SA Petaling Jaya, Selangor State, Malaysia] and Diamicron [Sevier, Bangkok, Thailand], with or without Metformin [Upha Corporation, Bangi, Selangor State, India]) that they took in common with the control group. OUTCOME MEASURES: Thirty-two (32) clinical variables were investigated, including liver enzymes, kidney function tests, hematologic parameters, blood glucose, insulin, and C-peptide assays. RESULTS: At the end of 3 months it was found that there was a significant decrease in the levels of fasting and postprandial blood glucose, cholesterol, triglycerides, glycated hemoglobin (Hb A(1C)) and fasting insulin in the treatment group compared to the controls. Cogent db did not alter the liver function tests, hematologic parameters, or the kidney function tests. CONCLUSIONS: These results concur with earlier animal studies that indicate that Cogent db is safe, reliable, tolerable, and efficacious in the control of type 2 diabetes mellitus.

Adult↗

PubMed2005

Prevalence of retinopathy in Caucasian type 2 diabetic patients from the South of Brazil and relationship with clinical and metabolic factors.

Diabetic retinopathy (DR) is a sight-threatening chronic complication of diabetes mellitus and is the leading cause of acquired blindness in adults. In this cross-sectional study, we investigated the prevalence of and the factors associated with DR in an analysis of 210 consecutive and unrelated Brazilian Caucasians with type 2 diabetes mellitus. Retinopathy was evaluated by ophthalmoscopy and/or biomicroscopy through dilated pupils. The relationship between clinical and metabolic variables and the presence of DR was assessed by logistic regression analysis. DR was detected in 99 of the 210 patients (47%). In the univariate logistic regression analyses, male sex, duration of diabetes, body mass index, glycated hemoglobin, C-peptide, LDL cholesterol, smoking, and albumin excretion rate were found to be associated with the presence of DR. However, the multiple logistic regression analysis showed that only duration of diabetes (odds ratio (OR) = 1.15, 95% CI = 1.09-1.22; P < 0.001), glycated hemoglobin (OR = 1.21, 95% CI = 1.01-1.46; P = 0.047) and albumin excretion rate > 100 microg/min (OR = 12.72, 95% CI = 3.89-41.56; P < 0.001) were independently associated with DR. Although DR was found to be frequent among Brazilian type 2 diabetic patients, its prevalence was within the range observed in other Caucasian populations. Our findings emphasize the need for good glycemic control in order to prevent or delay the onset of DR, since the most well-known risk factors for the development of this complication in type 2 diabetes mellitus, such as duration of diabetes, glycated hemoglobin and albumin excretion rate were independently related to DR.

Adult↗

PubMed2004

Plasma adiponectin levels and risk of myocardial infarction in men.

CONTEXT: Adiponectin, a recently discovered adipocyte-derived peptide, is involved in the regulation of insulin sensitivity and lipid oxidation and, purportedly, in the development of atherosclerosis and coronary heart disease in humans. OBJECTIVE: To assess prospectively whether plasma adiponectin concentrations are associated with risk of myocardial infarction (MI). DESIGN, SETTING, AND PARTICIPANTS: Nested case-control study among 18 225 male participants of the Health Professionals Follow-up Study aged 40 to 75 years who were free of diagnosed cardiovascular disease at the time of blood draw (1993-1995). During 6 years of follow-up through January 31, 2000, 266 men subsequently developed nonfatal MI or fatal coronary heart disease. Using risk set sampling, controls were selected in a 2:1 ratio matched for age, date of blood draw, and smoking status (n = 532). MAIN OUTCOME MEASURE: Incidence of nonfatal MI and fatal coronary heart disease by adiponectin level. RESULTS: After adjustment for matched variables, participants in the highest compared with the lowest quintile of adiponectin levels had a significantly decreased risk of MI (relative risk [RR], 0.39; 95% confidence interval [CI], 0.23-0.64; P for trend <.001). Additional adjustment for family history of MI, body mass index, alcohol consumption, physical activity, and history of diabetes and hypertension did not substantively affect this relationship (RR, 0.41; 95% CI, 0.24-0.70; P for trend <.001). Further adjustment for hemoglobin A1c or C-reactive protein levels also had little impact, but additional adjustment for low- and high-density lipoprotein cholesterol levels modestly attenuated this association (RR, 0.56; 95% CI, 0.32-0.99; P for trend =.02). CONCLUSIONS: High plasma adiponectin concentrations are associated with lower risk of MI in men. This relationship can be only partly explained by differences in blood lipids and is independent of inflammation and glycemic status.

Adiponectin↗

PubMed2006

Assessing glucose meter accuracy.

BACKGROUND: Self-monitoring of blood glucose plays an important role in the management of diabetes, particularly in patients treated with insulin. Blood glucose meters must have sufficient accuracy to allow patients and clinicians to monitor glycemic control and then modify treatment accordingly. Although several standards have been proposed, a consensus about how to measure glucose meter accuracy is not available. SCOPE: An informal review of recently published articles dealing with glucose meter accuracy was conducted to provide recommendations for evaluating accuracy relevant to the practicing clinician. FINDINGS: Whether in clinical practice or in accuracy studies, the accuracy of blood glucose meters is typically determined by comparing meter results to those obtained by a clinical laboratory method on samples collected from the same patient at the same time. However, multiple sample-related, analysis-related, and data display-related factors can have an impact on accuracy determination. Clinicians need to recognize these factors and take steps to minimize their impact when assessing the accuracy of glucose meters used by their patients. CONCLUSIONS: Although modern glucose meters show variable results with respect to analytical measures of accuracy, error grid analysis demonstrates that measurements deemed clinically acceptable approach 100%.

Blood Glucose Self-Monitoring↗

PubMed1989

[Standard meal substitute for oral glucose tolerance test in pregnancy].

The oral glucose tolerance test (OGTT) has been the recommended method of screening for the diagnosis of gestational diabetes. Based on the glycemic index of common foods, a standard meal was designed as a substitute meal test (SMT). It consisted of 3 slices of toast (75 g) with 60 g of jam, 11 g of sugar in a cup of tea, and 150 g of canned puree sweetened with sugar (8%), for a total of 118 g of available carbohydrate and a total of 518 cal. Plasma glucose concentrations of 46 pregnant women in the 2nd and 3rd trimesters were determined at 20 minute intervals for 3 hours after ingestion of this SMT, and were compared with those after a 100 g OGTT meal. There was a high correlation (r = 0.96, p less than 0.001) between comparable glucose concentrations after the 2 tests. With the SMT there were significantly fewer side-effects (nausea and vomiting), a higher level on preference scoring and reduced interassay variability of glucose levels after 2 hours. 6 gestational diabetics were diagnosed by the OGTT. In these patients glucose concentrations were higher than 3 standard deviations above the mean 2 hours after ingestion of the SMT. We propose the SMT as a side-effect-free, reliable and convenient alternative to the OGTT in pregnancy.

Blood Glucose↗

PubMed2000

The combination of insulin-like growth factor I and insulin-like growth factor-binding protein-3 reduces insulin requirements in insulin-dependent type 1 diabetes: evidence for in vivo biological activity.

Insulin-like growth factor-I (IGF-I) enhances insulin action in normal subjects and in patients with both type 1 and 2 diabetes; however, its administration is associated with significant side effects in a high percentage of patients. The coadministration of IGF binding protein-3 (IGFBP-3, the predominant IGF binding protein in serum) with IGF-I limits IGF-I inducible side effects, but it does not attenuate the ability of IGF-I to enhance protein synthesis and bone accretion; therefore, we determined whether IGF-I/IGFBP-3 would retain biological activity in type 1 DM and limit side effects associated with free IGF-I administration. Twelve patients received recombinant human IGF-I plus IGFBP-3 (2 mg/kg-day) by continuous sc infusion for 2 weeks. Each subject served as his own control; and, during a paired 2-week period, each received a placebo infusion. The order of the treatments was randomized. Subjects were placed on a constant caloric intake but were allowed to adjust insulin doses to maintain appropriate levels of glycemic control. Subjects measured blood glucose four times per day at home and kept a log of their insulin use. Frequent sampling for glucose, insulin, and GH was conducted during four inpatient study periods, one at the beginning and one at the end of each 2-week study interval. During IGF-I/IGFBP-3, insulin doses were reduced by 49%, and mean serum glucose was reduced by 23%. Free insulin levels obtained during frequent sampling in hospital fell 47% on IGF-I/IGFBP-3, compared with control, but showed no change with placebo. Concomitant glucose measurements did not differ in the two treatment groups. There was no change in body weight. Fructosamine levels decreased by 12%, but this was not significant (P < 0.1). Fasting triglyceride was unchanged, but cholesterol declined from 170 +/- 24 to 149 +/- 31 mg/dL (P < 0.05). IGFBP-2 (an IGF-I-dependent responsive variable) rose from 141 +/- 56 to 251 +/- 98 ng/mL (P < 0.01) on IGF-I/IGFBP-3. To analyze the mechanism by which IGF-I/IGFBP-3 might reduce insulin requirements, the change in serum GH was quantified. Mean GH levels were reduced by 72%, from 2.48 to 0.55 ng/mL (P < 0.001). An equal number (40%) of drug- and placebo-treated subjects had minor hypoglycemic episodes at home that required adjustment of insulin doses. No episode was classified as severe. In contrast to previous studies with free IGF-I, there were no cases of edema, headache, jaw pain, retinal edema, or Bell's palsy. No subject withdrew because of drug complications. These findings indicate that IGF-I/IGFBP-3 is biologically active on carbohydrate metabolism, as measured by a decrease in insulin requirements in patients with type 1 diabetes. Further studies will be required to determine the long-term safety and efficacy of this combination in patients with insulin resistance and diabetes.

Adult↗

PubMedDate not supplied

Glycemic control in patients with type I diabetes and normoalbuminuria after long diabetes duration.

The importance of glycemic control for the avoidance of micro- and macroalbuminuria after a diabetes duration of 20 years or more was studied in type I (insulin-dependent) diabetic patients diagnosed before an age of 31 years. Glycemic control was assessed as glycated hemoglobin for 5 years or more, on average 9.8 years with 3.2 measurements per year. Of the 197 included patients, 97 men and 100 women, 112 were normoalbuminuric, 45 had microalbuminuria (20-200 mg/L), and 40 had macroalbuminuria (persistent albuminuria > 200 mg/L). Normoalbuminuric patients had a mean HbA1c +/- SEM for the whole measurement period of 6.9 +/- 0.08%, the microalbuminuric patients 7.3 +/- 0.14% (Mann-Whitney test versus normoalbuminuric group, p = 0.025), and macroalbuminuric patients 7.6 +/- 0.13 (p < 0.001). The patients were on average 45 years old, and had an age at onset of 14 years, without significant differences between the groups. Thirteen patients had regressed from macroalbuminuria to normo- (n = 6) or microalbuminuria (n = 7). Of the normoalbuminuric patients, 43% were male, compared to 44% with microalbuminuria and 73% with macroalbuminuria (chi 2, p = 0.026). Logistic regression, with absence of albuminuria as dependent variable, showed a beneficial impact from lower HbA1c and normal blood pressure (blood pressure < 140/90 mm Hg without antihypertensive treatment). In conclusion, these results suggests that absence of albuminuria after 20 years or more of diabetes is associated with lower HbA1c.

Adult↗

PubMed2001

Platelet collagen receptor alpha2beta1 integrin and glycoprotein IIIa Pl(A1/A2) polymorphisms are not associated with nephropathy in type 2 diabetes.

Platelet glycoprotein receptors play a role in the pathogenesis of chronic diabetic complications. Genetic polymorphisms of the alpha2beta1 integrin and glycoprotein IIIa (GPIIIa) have been associated with myocardial infarction, stroke, and diabetic retinopathy. To identify risk factors for their development in a cohort of patients with type 2 diabetes, we evaluated clinical variables and genetic polymorphisms in the alpha2beta1 integrin and GPIIIa genes. Two hundred thirty-four subjects with type 2 diabetes (126 patients with and 108 patients without diabetic nephropathy), as well as 217 nondiabetic healthy subjects, were recruited for this study. Clinical factors for investigation included sex, age at diagnosis, duration of diabetes, body mass index (BMI), and fasting plasma glucose, hemoglobin A(1c) (HbA(1c)), total cholesterol, and triglyceride levels. Genotypes were determined by polymerase chain reaction and restriction fragment length polymorphism analyses. No difference in the Bgl II polymorphism of the alpha2beta1 integrin gene was found between patients with type 2 diabetes with or without nephropathy (11 [8.7%], 47 [37.3%], and 68 patients [54.0%] versus 10 [9.3%], 32 [29.6%], and 66 patients [61.1%] for Bgl II+/+, Bgl II+/-, and Bgl II-/-, respectively; P = 0.271). Multiple logistic regression analyses showed that duration of diabetes, BMI, hypertension, and poor glycemic control were four independent predictors for the development of diabetic nephropathy. No contribution of the Bgl II+ allele of the alpha2beta1 integrin was found for the risk for nephropathy (odds ratio, 1.258; 95% confidence interval, 0.655 to 2.418; P = 0.490). The Pl(A2) allele genotype was not found among our studied subjects. In conclusion, age, duration of diabetes, BMI, and HbA(1c) level are strong predictors for nephropathy in patients with type 2 diabetes. However, the Bgl II polymorphism of the alpha2beta1 integrin gene and the Apa I polymorphism of the platelet GPIIIa gene do not have a major role in the development of diabetic nephropathy in our population.

Blood Platelets↗

PubMed2000

Stress and metabolic control in diabetes mellitus: methodological issues and an illustrative analysis.

RATIONALE: The purpose of this article was twofold: a) to review studies of stress and glycemic control in diabetes, and b) to present a data analysis that illustrates the complexities of investigating stress in relation to blood glucose. The literature review emphasized human studies and the strengths and weaknesses of alternative designs. Special consideration was given to longitudinal investigations, and an analysis of data from the Diabetes Control and Complications Trial (DCCT) was presented to exemplify this approach. Nine individuals with Type 1 diabetes who participated in this project at the University of Iowa were studied over a period of 2 years. Stress was multiply measured (Life Experiences Survey, Hassles Scale, Perceived Stress Scale) as was blood glucose control (daily reflectance meter readings; monthly HbA1c). Within-subject time-series analyses and a combined longitudinal/cross-sectional model were used to analyze data. Two of the nine subjects manifested significant correlations between stress and HbA1c, and six subjects exhibited significant associations between stress and daily level or variability of glucose readings. The latter correlations varied in sign and appeared to cluster around specific individuals rather than a particular measure of stress or blood glucose. CONCLUSION: While the subjects may not represent the full spectrum of individuals with Type 1 diabetes, results were consistent with earlier longitudinal research in suggesting that the strength and direction of the relationship between stress and blood glucose control varies considerably between individuals.

Adult↗

PubMed2005

Progression of chronic kidney disease: can it be prevented or arrested?

Chronic kidney disease constitutes a highly prevalent health problem worldwide. Left untreated, it progresses inexorably to greater levels of severity at variable rates. The morbid impact of chronic kidney disease is heightened by its role as risk factor for cardiovascular disease. In the past two decades, considerable gains have been realized in retarding progression of chronic kidney disease by emphasizing blood pressure control and blockade of the renin-angiotensin system. Notwithstanding, the therapeutic goal of preventing or arresting chronic kidney disease progression remains unfulfilled. Currently attainable rates of decrease in glomerular filtration rate remain at 2 to 8 mL/min/y depending on the underlying disease. It is now believed that to achieve optimal therapeutic targets (proteinuria of <500 mg/day and decrease in glomerular filtration rate of 1 mL/min/y, the average age-related decline) we must introduce novel strategies and a multifaceted approach to treatment that interrupts multiple mechanisms of progression. To this end, and wherever relevant, new approaches to cause-specific treatment must be applied, such as targeted immunosuppression, intensive glycemic control, gene therapy, and enzyme replacement therapy. Furthermore, in all chronic kidney disease, we must interfere more effectively with the multitude of common mechanisms of progression. Established or putative, such approaches include aggressive blood pressure control; advanced renin-angiotensin system blockade; cytokine modulation and antifibrotic therapy; aldosterone blockade; endothelin blockade, nitric oxide modulation and vasopeptidase inhibition; antioxidant therapy; statin therapy; glycosaminoglycan therapy; anemia therapy; dietary restrictions; lifestyle changes; and pharmacogenomic profiling. Such a concerted, multifaceted approach to management might indeed prevent or arrest progression of chronic kidney disease, or even achieve regression of chronic kidney disease.

Anemia↗