Interference of elevated fetal hemoglobin on HbA1c measurements in adult type I diabetic patient.
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Aged↗
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Effects of metformin on insulin resistance, risk factors for cardiovascular disease, and plasminogen activator inhibitor in NIDDM subjects. A study of two ethnic groups.
OBJECTIVE: To investigate the effects of metformin on glycemic control, insulin resistance, and risk factors for cardiovascular disease in NIDDM subjects from two ethnic groups (Caucasian and Asian) with different risks of cardiovascular disease. RESEARCH DESIGN AND METHODS: A total of 27 subjects with NIDDM (17 Caucasian, 10 Asian) were given metformin and placebo each for a 12-wk period in a randomized, double-blind, placebo-controlled crossover study, and the dose was increased after 1 and 6 wk, up to a maximum of 850 mg three times a day. Insulin resistance, glycemic control, and cardiovascular risk factors were assessed before and after each treatment phase. The end of 12 wk of metformin treatment was compared with the end of 12 wk of placebo treatment. RESULTS: Metformin treatment was associated with significant improvement in FPG at 6 and 12 wk (mean difference at 12 wk, -3.08 mM, 95% CI -4.12 to -2.04 mM, P < 0.0001) and MCR of glucose (median difference 0.40 ml.kg-1.min-1, interquartile range -0.10 to 1.30 ml.kg-1.min-1, P = 0.036). beta-cell function calculated by HOMA also improved significantly (median difference 14%, interquartile range 7 to 23%, P < 0.001). Total triglyceride (median difference -0.2 mM, interquartile range -0.6 to 0.1 mM, P = 0.034), total cholesterol (mean difference -0.52 mM, 95% CI -0.83 to -0.22 mM, P = 0.002), and LDL cholesterol (mean difference -0.40 mM, 95% CI -0.64 to -0.16 mM, P = 0.002) fell significantly on metformin treatment, whereas no significant changes were observed in HDL cholesterol. PAI-1 activity fell significantly (mean difference -5.3 AU/ml, 95% CI -8.2 to -2.4 AU/ml, P = 0.001), but plasma fibrinogen concentrations and platelet function, spontaneous or agonist induced, were unaffected. UAE was lower on metformin treatment (median difference -2.4 micrograms/min, interquartile range -4.4 to -0.2 micrograms/min, P = 0.004), but metformin had no significant effect on BP. The effects of metformin on glycemic control and cardiovascular risk factors were generally similar in the two ethnic groups. CONCLUSIONS: These findings indicate that metformin treatment improves glycemic control, and lowers insulin resistance and risk factors for cardiovascular disease, including PAI-1, and may therefore be useful in the long-term management of NIDDM subjects who have a high risk of cardiovascular disease.
Albuminuria↗
Lipoprotein(a) levels in Japanese children with IDDM.
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Adolescent↗
Metabolic and hemodynamic effects of metformin and glibenclamide in normotensive NIDDM patients.
OBJECTIVE: To compare the metabolic and hemodynamic effects of metformin and glibenclamide in normotensive NIDDM patients. RESEARCH DESIGN AND METHODS: After a 2-wk run-in period on dietary treatment alone, 12 Chinese normotensive patients with uncomplicated NIDDM were randomized to receive either metformin, or glibenclamide for 4 wk before being crossed-over to the alternative treatment for an additional 4 wk. Metabolic and hemodynamic index, including cardiac output estimation by impedance cardiography, were measured at baseline and at the end of each treatment period. RESULTS: Body mass index was reduced more with metformin than with glibenclamide, although glycemic control was similar with both drugs. Plasma total cholesterol concentration fell more with metformin (mean difference -0.65 mM, 95% confidence interval -0.96 to -0.32) than glibenclamide (mean difference -0.20 mM, 95% confidence interval -0.54-0.12) (P < 0.05). Compared with baseline values, erect diastolic blood pressure was reduced more by metformin (12.9% [95% confidence interval -21.5 to -4.4%]) than glibenclamide (-6.8% [95% confidence interval -14.9 to 1.2%]) (P < 0.001). The relative changes in the systemic vascular resistance index also differed between the two treatments (glibenclamide, 6.2 [-4.3 to 16.6%]; metformin, -1.2 [95% confidence interval -8.8-6.4%]) (P < 0.05)]. CONCLUSIONS: In normotensive NIDDM patients, treatment with metformin was associated with greater reductions in body weight, plasma total cholesterol concentration, and erect diastolic blood pressure, whereas the systemic vascular resistance index increased after treatment with glibenclamide. These findings merit long-term investigation.
Biomarkers↗
Atrial natriuretic factor in hypertensive and normotensive diabetic patients.
OBJECTIVE: To evaluate plasma atrial natriuretic factor (ANF) behavior in hypertensive patients with either insulin-dependent (type I) or non-insulin-dependent (type II) diabetes. RESEARCH DESIGN AND METHODS: Plasma ANF levels were measured in euglycemic normotensive patients (n = 18) and hypertensive patients (n = 18), in diabetic normotensive patients (type I diabetes, n = 12; type II diabetes, n = 12), and in diabetic hypertensive patients (type I diabetes, n = 12; type II diabetes, n = 22). In all groups, plasma ANF levels were determined at the end of a normal NaCl diet period (120 mmol NaCl per day for 10 days) in both the supine and the upright positions. RESULTS: Plasma ANF levels were significantly higher (P < 0.05) in hypertensive euglycemic patients (supine vs. upright: 13.4 +/- 6.7 vs. 8.5 +/- 4.3 fmol/ml) than in normotensive type I diabetic patients (supine vs. upright: 8.6 +/- 2.2 vs. 5.9 +/- 2.9 fmol/ml) but not in euglycemic normotensive subjects (supine vs. upright: 11.4 +/- 5.1 vs. 7.6 +/- 5.8 fmol/ml) and normotensive type II diabetic patients (supine vs. upright: 10.1 +/- 4.1 vs. 7.9 +/- 4.1 fmol/ml). Moreover, in the normotensive groups plasma ANF levels did not significantly differ among euglycemic type I and type II diabetic patients. However, the highest levels of plasma ANF were observed in hypertensive type II diabetic patients (supine vs. upright: 16.9 +/- 7.4 fmol/ml [P < 0.01 vs. euglycemic normotensive subjects, P < 0.0001 vs. normotensive type I diabetic patients, P < 0.01 vs. hypertensive type I diabetic patients and normotensive type II diabetic patients] vs. 11.6 +/- 2.9 fmol/ml [P < 0.005 vs. normotensive type I diabetic patients, P < 0.01 vs. hypertensive type I diabetic patients]). On the contrary, plasma ANF levels were higher (P < 0.05) in hypertensive type I diabetic patients (supine vs. upright: 10.8 +/- 1.9 vs. 6.4 +/- 2.2 fmol/ml) compared with normotensive type I diabetic patients, but not with any other patient group. A significant correlation between supine ANF and insulin levels was found in both type II diabetic (r = 0.457; P < 0.05) and nondiabetic hypertensive patients (r = 0.716; P < 0.0001). CONCLUSIONS: These findings indicate that circulating ANF levels are markedly elevated in type II diabetic patients affected by essential hypertension. On the contrary, plasma ANF levels are in the range of normality in normotensive type I and type II diabetic patients.
Adult↗
Effect of a high-monounsaturated fat diet enriched with avocado in NIDDM patients.
OBJECTIVE: To assess the effects of two controlled diets, one rich in oleic acid obtained from avocado and olive oil and the other rich in complex carbohydrates, on fasting and postprandial serum lipids and glycemic control in 12 women with NIDDM. RESEARCH DESIGN AND METHODS: A randomized crossover study was designed. During a 4-week baseline period, all patients received the isocaloric diets recommended by the American Diabetes Association. After this period the patients were randomly assigned to receive the two study diets alternatively during two 4-week periods. One diet was high in monounsaturated fatty acids (HMUFA) and the other was high in complex carbohydrates (high-CHO). There also was a 4-week washout period in between the two 4-week periods during which the patients followed the American Diabetes Association's isocaloric diet. Blood samples were obtained before and after each dietary period. RESULTS: Both diets had a minor hypocholesterolemic effect with no major changes in high-density lipoprotein cholesterol. The HMUFA diet was associated with a greater decrement in plasma triglycerides (20 vs. 7% in the high-CHO diet). Glycemic control was similar with both diets. CONCLUSIONS: Partial replacement of complex digestible carbohydrates with monounsaturated fatty acids (avocado as one of its main sources) in the diet of patients with non-insulin-dependent diabetes mellitus improves the lipid profile favorably, maintains an adequate glycemic control, and offers a good management alternative.
Biomarkers↗
The effects of enalapril and nifedipine on carbohydrate and lipid metabolism in NIDDM.
OBJECTIVE: To compare the effects of nifedipine and enalapril on carbohydrate and lipoprotein metabolism in Chinese non-insulin-dependent diabetes mellitus (NIDDM) patients with hypertension. RESEARCH DESIGN AND METHODS: A 12-week, double-blind, randomized study of plasma lipid levels and glycemic control in patients treated with nifedipine (n = 52) or enalapril (n = 50) was conducted. None of the patients were treated with insulin. Diet and dosages of oral hypoglycemic agents remained unchanged during the 12-week treatment period. RESULTS: Mean arterial pressure was reduced more by nifedipine than by enalapril (23.1 vs. 11.1 mmHg, P < 0.001). Similar reductions in body mass index and plasma triglycerides and increases in apolipoprotein A-I were seen with both treatments, but HbA1 was reduced more during treatment with enalapril than with nifedipine (0.49 vs. 0.20%, P = 0.035) and serum apolipoprotein B (apoB) also declined more with enalapril than with nifedipine (8.2 vs. 2.3 mg/dl, P = 0.009). CONCLUSIONS: Twelve weeks of treatment with enalapril in hypertensive NIDDM patients was associated with greater improvement in glycemic control and greater reduction in serum apoB concentration, although the reduction in blood pressure was less than with nifedipine. These changes in cardiovascular risk profile warrant investigation for a longer term.
Apolipoprotein A-I↗
Impaired retinal artery blood flow in IDDM patients before clinical manifestations of diabetic retinopathy.
OBJECTIVE: To determine whether hemodynamic changes in retinal arteries precede clinical manifestations of diabetic retinopathy and to examine the effects of control of hyperglycemia on retinal artery blood flow. RESEARCH DESIGN AND METHODS: We assessed blood flow in bilateral central retinal arteries in 50 insulin-dependent diabetes mellitus (IDDM) patients without retinopathy and 20 sex- and age-matched control subjects using duplex Doppler sonography. We determined the peak systolic velocity (PSV), end-diastolic velocity (EDV), time-averaged velocity (TAV), resistance index (RI), and pulsatility index (PI). RESULTS: PSV, EDV, and TAV were significantly lower in IDDM patients than in control subjects (P < 0.05, P < 0.01, and P < 0.01, respectively). The RI was significantly higher in IDDM patients than in control subjects (P < 0.01) and was significantly correlated with plasma levels of glucose in IDDM patients (r = 0.0.310, P = 0.0248). Multiple regression analysis identified the plasma levels of glucose as a significant determination of RI in IDDM patients. After 14 days of intensive insulin therapy in 7 IDDM patients, the RI and plasma levels of glucose showed significant decreases (P = 0.018, P = 0.001, respectively). CONCLUSIONS: Our results showed that changes in retinal hemodynamics were present before the clinical detection of overt diabetic retinopathy and suggest that the presence of short-term hyperglycemia partly contributes to impaired retinal circulation.
Adolescent↗
Impaired glucose tolerance leads to delayed diagnosis of Alström syndrome.
OBJECTIVE: To emphasis the need for timely diagnosis of Alström syndrome. CASE: We report a case of late-detected Alström syndrome in a boy 15 1/2 years of age who was admitted because of poor wound healing and hyperglycemia. RESULTS: Diagnosis was made and the patient's impaired glucose tolerance improved by diet. CONCLUSIONS: Regular follow-ups are needed to recognize and possibly prevent late-appearing complications.
Adolescent↗
Effects of Vitamin E on susceptibility of low-density lipoprotein and low-density lipoprotein subfractions to oxidation and on protein glycation in NIDDM.
OBJECTIVE: To evaluate the effect of vitamin E supplementation on the susceptibility of low-density lipoprotein (LDL) and LDL subfractions to oxidation and on protein glycation in non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS: Twenty-one men with NIDDM (HbA1c = 6-10%), ages 50-70, were randomly assigned to either 1,600 IU/day of vitamin E or placebo for 10 weeks after a 4-week placebo period. LDL and LDL subfractions were isolated after 4 weeks of placebo and after 6 and 10 weeks of therapy. Susceptibility of LDL to copper-mediated oxidation was measured by conjugated diene formation (lag time) and formation of thiobarbituric acid-reactive substances (TBARS). Fasting serum glucose, mean weekly blood glucose, HbA1c, and glycated plasma protein concentrations were also determined at these time points. RESULTS: Vitamin E content in plasma and LDL increased 4.0- and 3.7-fold, respectively, in the vitamin E-treated group. Vitamin E decreased the susceptibility of LDL to oxidation in comparison with placebo (lag time, 243 +/- 46 vs. 151 +/- 22 min, P < 0.01; 3 h TBARS, 24 +/- 12 vs. 66 +/- 18 nmol malondialdehyde/mg LDL, P < 0.05). Vitamin E content also increased significantly in both buoyant and dense LDL subfractions, and their oxidation was dramatically reduced. The lag time of LDL oxidation correlated well with the content of vitamin E in both LDL and its subfractions (r = 0.69-0.92). Glycemic indexes did not change significantly in either group during the study. Protein glycation, including glycated hemoglobin, glycated albumin, glycated total plasma proteins, and glycated LDL were unchanged in the vitamin E group. CONCLUSIONS: Supplementation of vitamin E in NIDDM leads to enrichment of LDL and LDL subfractions and reduced susceptibility to oxidation. Despite a greater percentage increase in vitamin E content in small dense LDL, it remained substantially more susceptible to oxidation than was buoyant LDL. This suggests that dense, LDL may gain less protection against oxidation from antioxidant supplementation than does larger, more buoyant LDL. In contrast to previous reports, vitamin E supplementation did not reduce glycation of intracellular or plasma proteins.
Aged↗
Similar insulin sensitivity in NIDDM patients with normo- and microalbuminuria.
OBJECTIVE: To investigate whether insulin resistance and microalbuminuria are associated in non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS: Insulin sensitivity was assessed using a hyperinsulinemic euglycemic clamp in 11 normoalbuminuric and 9 microalbuminuric NIDDM patients matched for sex, age, body composition, glycemic control, diabetes duration, and therapy. RESULTS: Isotopically determined glucose disposal was similar in normo- and microalbuminuric patients in the basal state (mean +/- SD; 3.30 +/- 1.01 vs. 3.46 +/- 0.82 mg.kg lean body mass [LBM]-1.min-1; NS) and during hyperinsulinemia (7.16 +/- 2.65 vs. 6.63 +/- 2.88 mg.kg LBM-1.min-1;NS). No difference was observed in nonoxidative glucose disposal or lipid oxidation. Endogenous glucose production was equally suppressed by insulin (-0.08 +/- 0.99 vs. 0.30 +/- 1.12 mg.kg-1 LBM.min-1; NS). Glucose oxidation tended to be lower in the normoalbuminuric patients in the basal state (1.16 +/- 0.37 vs. 1.41 +/- 0.36 mg.kg LBM-1.min-1) and during hyperinsulinemia (2.35 +/- 0.72 vs. 2.90 +/- 0.77 mg.kg LBM-1.min-1; both P < 0.15). Urinary albumin excretion rate correlated with the insulin-stimulated glucose oxidation rate (r = 0.59, P = 0.0064), and a similar trend was seen in the basal state (r = 0.42, P = 0.063). Protein oxidation was higher in normoalbuminuric patients (1.6 +/- 0.5 vs. 1.0 +/- 0.4 mg.kg LBM-1.min-1; P = 0.017) and correlated inversely with albuminuria (r = -0.70, P = 0.0007). Serum growth hormone increased during insulin infusion; however, the increase was significantly greater in microalbuminuric patients. Plasma lipoproteins, maximal aerobic capacity, and 24-h ambulatory blood pressure were similar in the two groups. CONCLUSIONS: Basal and insulin-stimulated glucose uptakes are comparable in carefully matched normo- and microalbuminuric NIDDM patients, and glucose oxidation may be positively related to albuminuria. The inverse relation between protein oxidation and albuminuria may be due to higher growth hormone levels during daily life perturbations in glucose in microalbuminuric patients.
Albuminuria↗
Noninvasive detection of functional alterations of the arterial wall in IDDM patients with and without microalbuminuria.
OBJECTIVE: To test endothelial function in a group of 10 normoalbuminuric and eight microalbuminuric insulin-dependent diabetes mellitus patients (ages 28 +/- 3 [mean +/- SE] and 28 +/- 1 years, respectively), in comparison with 16 control subjects (age 35 +/- 2 years, normal subjects vs. diabetic subjects P = NS), to identify prestructural abnormalities of the arterial wall. An early stage of vascular involvement seems in fact to be characterized by functional alterations of endothelial control on vascular tone and wall interaction with circulating cells. Furthermore, many recent studies suggest the importance of microalbuminuria as an early marker not only of nephropathy but also of retinopathy and macroangiopathy. RESEARCH DESIGN AND METHODS: Endothelium-mediated flow-dependent vasodilation and endothelium-independent vasodilation (induced by glyceryl trinitrate administration) were evaluated in the right common femoral artery by echo-Doppler ultrasound. Arterial wall distensibility was evaluated at the common femoral artery by an echo-tracking system. RESULTS: In spite of a comparable increase in flow velocity, endothelium-mediated vasodilation was significantly reduced in diabetic subjects, particularly in microalbuminuric patients. Endothelium-independent vasodilation was also significantly impaired in diabetic subjects, particularly in microalbuminuric subjects; whereas arterial wall distensibility, an index of the viscoelastic properties of the wall, was similar in the three groups. CONCLUSIONS: These results confirm a reduced vasodilatory capacity in diabetes mellitus, with a more marked alteration in microalbuminuric diabetic subjects. This reliable, noninvasive evaluation of arterial function is particularly useful for early diagnosis of vascular involvement.
Adult↗
Lipoprotein(a), apolipoprotein(a) polymorphism, and insulin treatment in type II diabetic patients.
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Administration, Oral↗
Increase in circulating products of lipid peroxidation in smokers with IDDM.
OBJECTIVE: To measure plasma malondialdehyde (MDA) concentration, a product of lipid peroxidation, both in IDDM patients and in healthy control subjects and to examine whether smoking has a negative impact on the plasma MDA levels in diabetic patients. RESEARCH DESIGN AND METHODS: Plasma total MDA concentration (as a thiobarbituric acid adduct by high-performance liquid chromatography) was measured in 56 young IDDM patients and in a group of 32 age-, sex-, BMI-, and smoking habit-matched healthy subjects. RESULTS: Plasma MDA concentration in IDDM patients was significantly higher than that in healthy control subjects (mean +/- SE: 0.95 +/- 0.03 vs. 0.54 +/- 0.03 mumol/l; P < 0.0001). After stratification by smoking status, it was seen that diabetic smokers had values of age, BMI, serum lipids, blood pressure, metabolic control, and diabetes duration and its chronic complications superimposable on those of their nonsmoking counterparts. Nevertheless, plasma MDA concentration was significantly higher in IDDM patients who smoked than in IDDM patients who didn't smoke (1.03 +/- 0.4 vs. 0.87 +/- 0.03 mumol/l; P = 0.002), without any sex difference with regard to MDA levels. CONCLUSIONS: These data show an increase in circulating products of lipid peroxidation in young diabetic smokers, thus further supporting the clinical importance of discouraging the initiation of smoking as well as promoting its cessation in people with IDDM.
Adult↗
Comparison of different insulin regimens in elderly patients with NIDDM.
OBJECTIVE: To compare the metabolic effects of three different frequently used regimens of insulin administration on blood glucose control and serum lipids, and the costs associated with this treatment, in subjects with NIDDM, who were poorly controlled with oral antihyperglycemic agents. RESEARCH DESIGN AND METHODS: We studied 95 elderly patients with NIDDM (age 68 +/- 9 years, BMI 26.0 +/- 4.6 kg/m2, and median time since diagnosis of diabetes 9 years [range 1-37]; 37 men, 58 women), who were poorly controlled, despite diet and maximal doses of oral antihyperglycemic agents. Three insulin administration regimens were compared during a 6-month period: patients were randomized for treatment with a two-injection scheme (regimen A) or a combination of glibenclamide with one injection of NPH insulin, administered either at bedtime (regimen B) or before breakfast (regimen C), and insulin treatment was mainly instituted in an outpatient setting. RESULTS: After 6 months of insulin treatment, fasting blood glucose of the total patient population had decreased from an average of 14.1 +/- 2.2 to 8.3 +/- 2.0 mmol/L (P < 0.001), and HbA1c fell from 11.0 +/- 1.3 to 8.3 +/- 1.2% (P < 0.001); 34 patients reached HbA1c levels below 8.0%, 25 of them even below 7.5%. With two insulin injections daily, HbA1c decreased from 11.2 +/- 1.3 to 8.2 +/- 1.2%, while during combined treatment, HbA1c fell from 10.5 +/- 1.2 to 8.1 +/- 1.1% (regimen B) and from 11.1 +/- 1.3 to 8.5 +/- 1.1% (regimen C). Comparable improvement of the other measures of glycemic control, lipids and lipoproteins, was observed in the different treatment regimens. Body weight increase was moderate (mean +/- 4.0 kg) and similar in all patient groups. One-third of patients starting with one insulin injection daily needed a second injection to control glycemia. One episode of severe hypoglycemia was observed. Combined insulin-sulfonylurea treatment was almost 20% more expensive than twice-daily administration of insulin alone. CONCLUSIONS: Insulin treatment can safely be instituted in elderly patients with NIDDM. However, it is difficult to obtain optimal glycemic control. Insulin has moderate beneficial effects on serum lipoproteins. Although on the basis of glycemic control and weight gain, no preference for any treatment regimen can be discerned, twice-daily insulin administration is the most simple and cost-effective regimen.
Aged↗
Oxidative stress at onset and in early stages of type 1 diabetes in children and adolescents.
OBJECTIVE: In diabetes, the persistence of hyperglycemia has been reported to cause increased production of oxygen free radicals through glucose autooxidation and nonenzymatic glycation. The aim of this study was to determine whether oxidative cellular damage occurs at the clinical onset of diabetes and in later stages of the disease in young patients. RESEARCH DESIGN AND METHODS: Indicative parameters of lipoperoxidation, protein oxidation, and changes in the status of antioxidant defense systems were evaluated in single blood samples from 54 diabetic children, adolescents, and young adults and 60 healthy age- and sex-matched control subjects. RESULTS: Malondialdehyde and protein carbonyl group levels in plasma were progressively higher in diabetic children and adolescents than in control subjects (P < 0.0001). The highest erythrocyte superoxide dismutase (SOD) activity was found in diabetic children at onset of clinical diabetes. In diabetic adolescents, SOD was also significantly higher (P < 0.0001) than in control subjects. Erythrocyte glutathione peroxidase was significantly lower in diabetic children and adolescents compared with control subjects (P < 0.002). A significant decline in blood glutathione content at the recent onset of diabetes was found (P < 0.0001). Furthermore, our results demonstrated progressive glutathione depletion during diabetes evolution. The plasma alpha-tocopherol/total lipids ratio and beta-carotene levels during diabetes development (P < 0.001) were low. CONCLUSIONS: This cross-sectional study in young diabetic patients showed that systemic oxidative stress is present upon early onset of type 1 diabetes and is increased by early adulthood. Decreased antioxidant defenses may increase the susceptibility of diabetic patients to oxidative injury. Appropriate support for enhancing antioxidant supply in these young diabetic patients may help prevent clinical complications during the course of the disease.
Adolescent↗
Diabetic nephropathy in hypertransfused patients with beta-thalassemia. The role of oxidative stress.
OBJECTIVE: Pathogenesis of diabetes-related microvascular complications involving oxidative damage by free radicals has been demonstrated. Free radical generation has been shown to derive largely from iron. Our objectives, therefore, were to determine if there is an increased incidence and/or an accelerated course of nephropathy in patients with diabetes, secondary to transfusional hemochromatosis, and to examine whether free radical activity contributes to the development of this complication. RESEARCH DESIGN AND METHODS: We evaluated nine patients with homozygous beta-thalassemia, complicated by clinically overt diabetes, for diabetic nephropathy over a 7-year period. Lipid peroxidation was quantified by measuring the presence of 20 saturated and unsaturated aldehydes, and results were compared with five normotensive type 1 diabetic patients without iron overload. RESULTS: Nephropathy developed in five of nine patients (55%) after a mean duration of overt diabetes of 3.6 +/- 2.0 years. Three patients showed evidence of progressive microalbuminuria over a 7-year period (24.7-46.2, 52.2-430.1, and 17.7-54.3 micrograms/min, respectively). Two patients with borderline microalbuminuria (19.9 and 14.5 micrograms/min, respectively) demonstrated stable albumin excretion rates over the follow-up period. Total aldehyde concentration was significantly higher in beta-thalassemia diabetic patients, compared with nonthalassemic diabetic control subjects (8,106 +/- 1,280 vs. 4,594 +/- 247 nmol/l; P < 0.0001). The three patients with progressive microalbuminuria demonstrated significantly higher total aldehyde concentration, compared with the other beta-thalassemia diabetic patients with stable albumin excretion (9,428 +/- 337 vs. 7,445 +/- 1,003 nmol/l; P < 0.01). Serum vitamin E concentrations were significantly lower in beta-thalassemia patients with diabetes, compared with diabetic patients without iron overload (12.1 +/- 6.0 vs. 25.9 +/- 11.4 mumol/l; P = 0.02). Serum vitamin C concentrations did not differ between the two groups. Multiple regression analysis demonstrated total aldehyde concentration to be the most significant predictor for the development of microalbuminuria (P = 0.01), followed by the duration of diabetes (P = 0.02) and glycemic control (P = 0.02). CONCLUSIONS: Early development and an accelerated course of diabetic nephropathy in iron-loaded patients with beta-thalassemia are observed. These findings may be attributed to high oxidative stress in these patients, which is secondary to iron-derived free radicals and to the patients' diminished antioxidant reserves.
Adult↗
Plasma lipoprotein(a) levels are not influenced by glycemic control in type 1 diabetes.
OBJECTIVE: To determine the influence of glycemic control improvement with intensive therapy on lipoprotein(a) [Lp(a)] concentrations in type 1 diabetic patients. RESEARCH DESIGN AND METHODS: A total of 105 poorly controlled type 1 diabetic patients (60 men, 45 women) without diabetic complications participated in a longitudinal study performed in a tertiary referral center, to compare lipid, lipoprotein, and Lp(a) levels before and after 3 months of intensive therapy with multiple insulin doses. Lp(a) levels were measured by the Terumo method. Differences between the two periods were assessed by the paired t test and Wilcoxon's test. RESULTS: After 3 months of intensive therapy, all patients exhibited improved glycemic control. HbA1c decreased from 8.9 +/- 2.4 to 6.5 +/- 1.6% (P < 0.0001), being < or =6% in 47% of patients. However, although a more favorable lipoprotein profile was obtained, no changes in Lp(a) concentrations were observed in the whole group of patients (16.7 +/- 17.3 vs. 17.2 +/- 17.7 mg/dl) or in patients with baseline Lp(a) levels above 30 mg/dl (47.1 +/- 14.8 vs. 47.4 +/- 18.9 mg/dl) or below 30 mg/dl (9.6 +/- 7.3 vs. 10.2 +/- 6.7 mg/dl). In addition, patients reaching HbA1c < or =6 or >6% presented similar Lp(a) levels (19.7 +/- 18.0 vs. 15.0 +/- 17.4 mg/dl), and changes in Lp(a) did not correlate with those observed in HbA1c. CONCLUSIONS: These data demonstrate that the improvement of glycemic control does not influence plasma Lp(a) concentrations in type 1 diabetic patients independently of baseline Lp(a) levels and the degree of glycemic control.
Adult↗