Biomedical subjects

Per-Henrik Groop

Publications and source records attributed to Per-Henrik Groop.

At least 19 recordsLinked to original sources

PubMed2007

A functional polymorphism in the manganese superoxide dismutase gene and diabetic nephropathy.

Oxidative stress has been suggested to contribute to the development of diabetic nephropathy. Manganese superoxide dismutase (MnSOD) protects the cells from oxidative damage by scavenging free radicals. The demand for antioxidants is increased by smoking, which could disturb the balance between antioxidants and radicals. The present study aimed to determine whether a valine/alanine polymorphism in MnSOD (V16A, rs4880), alone or in combination with smoking, can contribute to development of diabetic nephropathy in 1,510 Finnish and Swedish patients with type 1 diabetes. Overt diabetic nephropathy (n = 619) was defined as having an albumin excretion rate (AER) >200 microg/min or renal replacement therapy; incipient diabetic nephropathy was defined as having an AER of 20-200 microg/min (n = 336). The control subjects had diabetes duration of >or=20 years, without albuminuria (AER <20 microg/min) and without antihypertensive treatment (n = 555). In addition to male sex and elevated A1C, smoking was significantly associated with diabetic nephropathy (overt plus incipient), odds ratio (OR) 2.00 (95% CI 1.60-2.50). When controlling for age at onset, diabetes duration, A1C, smoking, and sex, the Val/Val genotype was associated with an increase in risk of diabetic nephropathy (1.32 [1.00-1.74], P = 0.049). When evaluating the combined effect of genotype and smoking, we used logistic regression with stratification according to smoking status and genotype. The high-risk group (ever smoking plus Val/Val genotype) had 2.52 times increased risk of diabetic nephropathy (95% CI 1.73-3.69) compared with the low-risk group, but no departure from additivity was found. Our results indicate that smoking and homozygosity for the MnSOD Val allele is associated with an increased risk of diabetic nephropathy, which supports the hypothesis that oxidative stress contributes to the development of diabetic nephropathy.

Adult↗

PubMed2006

Diagnosing diabetic nephropathy by 1H NMR metabonomics of serum.

OBJECT: The most severe complication of type 1 diabetes (T1DM) is diabetic nephropathy. It is associated with a high risk of cardiovascular complications and premature death and requires early detection to be efficiently treated. The clinical practice to diagnose diabetic nephropathy is also a non-optimal and tedious set up based on albumin excretion rate in multiple overnight or 24h urine samples. Conversely, in this study, these independent diagnostic data are used to provide a realistic testing case for applying (1)H NMR metabonomics of serum in a diagnostic fashion. MATERIALS AND METHODS: 182 T1DM and 21 non-diabetic (non-T1DM) individuals were studied. The (1)H NMR of serum at 500 MHz was targeted at two molecular windows: lipoprotein lipids and low-molecular-weight metabolites. RESULTS: T1DM and non-T1DM individuals were exclusively separated by (1)H NMR. For diabetic nephropathy diagnosis in the T1DM patients, (1)H NMR data (and clinical biochemistry data) gave a sensitivity of 87.1% (83.9%) and a specificity of 87.7% (95.9%). The predictive values of positive and negative tests were 89.0% (95.5%) and 83.6% (79.2%), respectively. CONCLUSIONS: (1)H NMR metabonomics clearly distinguishes metabolic characteristics of T1DM and appears approximately as good a means to diagnose diabetic nephropathy from serum as an advanced set of biochemical variables.

Biomarkers↗

PubMed2006

Low birth weight does not increase the risk of nephropathy in Finnish type 1 diabetic patients.

BACKGROUND: Low birth weight (LBW) has been linked to renal disease both in animal models and human studies. However, the role of birth weight in the development of diabetic nephropathy is unclear. We, therefore, studied the impact of birth weight on the development of diabetic nephropathy and other related traits, such as diabetic retinopathy and macrovascular disease, in Caucasian type 1 diabetic patients. METHODS: Data on size at birth were obtained from original birth certificates in 1543 Finnish patients with type 1 diabetes. The patients were divided into those with low (LBW; below the 10th percentile), normal (NBW; 11-90th percentile) and high birth weight (HBW; above the 90th percentile). RESULTS: Diabetic nephropathy was equally common in the groups with various birth weight (LBW vs NBW vs HBW: 21 vs 20 vs 17%, P = NS). End-stage renal disease (3 vs 5 vs 4%, P = NS), laser-treated retinopathy (31 vs 31 vs 31%, P = NS) and macrovascular disease (5 vs 5 vs 8%, P = NS) were equally prevalent in the various birth weight groups. The time from the onset of diabetes to the onset of diabetic nephropathy was similar irrespective of birth weight (log-rank test; P = NS). CONCLUSIONS: Based on our cross-sectional data, LBW does not have an impact on the development of diabetic nephropathy, laser-treated retinopathy or macrovascular disease later in life in Caucasians with type 1 diabetes.

Adult↗

PubMed2006

Association analysis of the AIRE and insulin genes in Finnish type 1 diabetic patients.

Mutations in the autoimmune regulator (AIRE) gene cause a recessive Mendelian disorder autoimmune polyendocrinopathy syndrome type 1 (APS-1 or autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy). APS-1 patients develop multiorgan autoimmune diseases including type 1 diabetes (prevalence 12%). The AIRE protein controls the central tolerance induction in the thymus by regulating the expression levels of tissue-specific peripheral antigens, such as insulin. We hypothesized that the insulin gene (INS) polymorphisms together with the AIRE variations may predispose individuals to diabetes. The role of the AIRE gene was tested both independently and on the condition of the INS risk genotype in the Finnish type 1 diabetes sample. A total of 733 type 1 diabetic cases and 735 age- and sex-matched healthy controls were used in the analysis. Five common single nucleotide polymorphisms (SNPs) in the AIRE gene were selected from the public database (dbSNP). The -23HphI polymorphism was used as a surrogate marker for the INS gene promoter repeat. The five genotyped SNPs in the AIRE gene showed no evidence of association with type 1 diabetes. As expected, the INS gene polymorphism -23HphI was significantly associated with susceptibility to type 1 diabetes (P=6.8 x 10(-12), chi(2) test). When the subclass of patients carrying the homozygote genotype of the INS gene was used in the analysis, the AIRE polymorphisms showed no association with the disease. In conclusion, the AIRE gene does not seem to contribute to disease susceptibility in Finnish type 1 diabetic patients, whereas the insulin gene represents a notable risk factor for disease in this population.

Adult↗

PubMed2006

VEGF gene variability and type 1 diabetes: evidence for a protective role.

Vascular endothelial growth factor (VEGF) is a multifunctional cytokine originally described as an angiogenic factor. A number of reports have recently demonstrated that VEGF increases pancreatic islet survival after islet transplantation by stimulating angiogenesis and improving islet revascularization. Whether VEGF can protect from the autoimmune destruction of insulin-producing beta-cells that characterizes the development of type 1 diabetes is presently unknown. To clarify this issue, we studied the association of three polymorphisms of the promoter region of VEGF with type 1 diabetes in the Italian and the Finnish populations. The polymorphisms considered [C(-2578)A, G(-1190)A, and G(-1154)A] are known to modulate in vitro and in vivo VEGF expression. We found that VEGF promoter genotypes are associated with type 1 diabetes in both populations, but with different combinations. In Italian individuals, the -2578AA and -1190AA genotypes are associated with type 1 diabetes and accelerate its onset, while in Finnish individuals, -1154GG and -1190GG protect from type 1 diabetes and delay its onset. In conclusion, because the expected functional consequence of both genotype combinations is a reduced VEGF expression in diabetic patients, we propose a protective role of VEGF in the development of type 1 diabetes.

Adult↗

PubMed2006

A quality assessment survey of SNP genotyping laboratories.

To survey the quality of SNP genotyping, a joint Nordic quality assessment (QA) round was organized between 11 laboratories in the Nordic and Baltic countries. The QA round involved blinded genotyping of 47 DNA samples for 18 or six randomly selected SNPs. The methods used by the participating laboratories included all major platforms for small- to medium-size SNP genotyping. The laboratories used their standard procedures for SNP assay design, genotyping, and quality control. Based on the joint results from all laboratories, a consensus genotype for each DNA sample and SNP was determined by the coordinator of the survey, and the results from each laboratory were compared to this genotype. The overall genotyping accuracy achieved in the survey was excellent. Six laboratories delivered genotype data that were in full agreement with the consensus genotype. The average accuracy per SNP varied from 99.1 to 100% between the laboratories, and it was frequently 100% for the majority of the assays for which SNP genotypes were reported. Lessons from the survey are that special attention should be given to the quality of the DNA samples prior to genotyping, and that a conservative approach for calling the genotypes should be used to achieve a high accuracy.

Clinical Laboratory Techniques↗

PubMed2006

Glu298Asp and NOS4ab polymorphisms in diabetic nephropathy.

BACKGROUND AND AIMS: The risk of diabetic nephropathy (DN) increases with increase in intraglomerular pressure, which may partly be regulated by nitric oxide (NO). NO-production can be affected by polymorphisms in the endothelial NO-synthase gene (NOS3), hyperglycaemia and smoking. We therefore studied association between DN and two polymorphisms in NOS3, Glu298Asp and NOS4ab, in Caucasian type 1 diabetes (T1D) patients. PATIENTS AND METHODS: A total of 1510 Finnish and Swedish T1D patients were included in a cross-sectional case-control study. Incipient DN was defined as an albumin excretion rate (AER) of 20-200 microg/min (n = 336). Overt DN = AER>200 microg/min or renal replacement therapy (n = 619). All patients with DN were considered as cases. The controls were T1D patients with diabetes duration 20 years, AER<20 microg/min and without antihypertensive treatment (n = 555). The genetic markers studied were a 27 bp repeat (NOS4ab) and Glu298Asp (rs1799983). RESULTS: Age at onset of diabetes, male sex, duration of diabetes, HbA1c, blood pressure and smoking were assessed as possible confounders in the logistic regression analysis, which showed that homozygosity for the Glu-allele of the Glu298Asp-polymorphism was independently associated with increased risk of DN (OR = 1.46; 95% CI = 1.12-1.91). The variables smoking (OR = 2.13; 95% CI = 1.63-2.78), male sex (OR = 1.61; 95% CI = 1.23-2.10), HbA1c (OR per % increase above upper limit of the normal reference range = 1.02; 95% CI = 1.02-1.03), systolic (OR = 1.05; 95% CI = 1.04-1.06) and diastolic blood pressure (OR = 1.04; 95% CI = 1.02-1.05) also significantly and independently increased the risk of DN when taking age at diabetes onset and diabetes duration into account. The NOS4 a-allele was not associated with DN. CONCLUSIONS: The Glu/Glu-genotype of the NOS3 Glu298Asp polymorphism may increase the risk of developing DN independently of other known risk factors.

Adult↗

PubMed2006

Impaired vascular dilatation in women with a history of pre-eclampsia.

OBJECTIVE: The mechanisms underlying increased cardiovascular risk among women with a history of pre-eclampsia remain unclear. Impaired endothelial function has been observed in both pre-eclampsia and atherosclerosis, and provides a plausible link between the two conditions. We studied endothelial function and arterial compliance in non-pregnant, previously pre-eclamptic women. DESIGN: A study of 30 women with a history of pre-eclampsia and 21 women with a previous normotensive, uncomplicated pregnancy was carried out. METHODS: Changes in brachial artery blood flow, induced by intra-arterial infusions of an endothelium-independent (sodium nitroprusside) and an endothelium-dependent (acetylcholine) vasodilator, were measured by venous occlusion plethysmography. Arterial stiffness was assessed by pulse-wave analysis. RESULTS: Vasodilatation was impaired in women with previous pre-eclampsia; at low and high concentrations of endothelium-independent (P = 0.004 and P = 0.057, respectively) and endothelium-dependent (P = 0.045 and P = 0.02) vasodilators, respectively. There was no difference in arterial stiffness between the groups (P = 0.45). In multiple regression analyses both endothelium-independent and endothelium-dependent vasodilatations were independently associated with a history of pre-eclampsia and parity. There was no correlation with blood pressure, body mass index (BMI), smoking or age. CONCLUSIONS: The finding of impaired vascular dilatation several years after a pre-eclamptic pregnancy could contribute to the higher risk of cardiovascular disease in these women.

Acetylcholine↗

PubMed2006

Analysis of 14 candidate genes for diabetic nephropathy on chromosome 3q in European populations: strongest evidence for association with a variant in the promoter region of the adiponectin gene.

Linkage studies have mapped loci for diabetic nephropathy and associated phenotypes on chromosome 3q. We studied 14 plausible candidate genes in the linkage region because of their potential role in vascular complications. In a large-scale study of patients from Denmark, Finland, and France who have type 1 diabetes, 1,057 case and 1,127 control subjects, as well as 532 trios, were investigated for association with diabetic nephropathy. We analyzed 69 haplotype-tagging single nucleotide polymorphisms and nonsynonymous variants that were identified by sequencing. Polymorphisms in three genes, glucose transporter 2 (SLC2A2), kininogen (KNG1), and adiponectin (ADIPOQ), showed nominal association with diabetic nephropathy in single-point analysis. The T-allele of SLC2A2_16459CT was associated with a decreased risk of diabetic nephropathy (odds ratio 0.79 [95% CI 0.66-0.96], P = 0.016), whereas the T-allele of KNG_7965CT and the A-allele of ADIPOQ_prom2GA were associated with increased risk of nephropathy (1.17 [1.03-1.32], P = 0.016; 1.46 [1.11-1.93], P = 0.006, respectively). Analyses of the transmission disequilibrium test showed similar trends only for ADIPOQ_prom2GA with the overtransmission of the A-allele to patients with diabetic nephropathy (1.52 [0.86-2.66], P = NS) and of the G-allele to patients without diabetic nephropathy (0.50 [0.27-0.92], P = 0.026). The overall significance for this variant (nominal P = 0.011) suggests that ADIPOQ might be involved in the development of diabetic nephropathy.

Chromosome Mapping↗

PubMed2006

Serum lipids and the progression of nephropathy in type 1 diabetes.

OBJECTIVE: Dyslipidemia contributes to the progression of microvascular disease in diabetes. However, different lipid variables may be important at different stages of nephropathy. This study examines the pattern of dyslipidemia associated with the progression of nephropathy in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: A total of 152 patients with type 1 diabetes were recruited in order to represent various phases of nephropathy. Patients were followed for 8-9 years, during which time they received standard care. Renal progression was defined a priori as a doubling in albumin excretion (in patients with normo- or microalbuminuria) or a decline in creatinine clearance (in those with macroalbuminuria). A panel of lipid variables was determined and correlated with indexes of progression. RESULTS: In patients with normoalbuminuria (n = 66), progression was associated with male sex (P < 0.05), borderline albuminuria (P = 0.02), and LDL-free cholesterol (P = 0.02). In patients with microalbuminuria (n = 51), progression was independently associated with triglyceride content of VLDL and intermediate-density lipoprotein (both P < 0.05). In patients with macroalbuminuria (n = 36), a significant decline in the renal function (>3 ml x min(-1) x year(-1)) was independently associated with poor glycemic control, hypertension, and LDL size (P < 0.05). When all patients with progressive nephropathy were analyzed together, only LDL cholesterol was predictive on multivariate analysis (P < 0.05), which masked the importance of triglyceride enrichment in microalbuminuria. CONCLUSIONS: Lipid variables are associated with progression of diabetic kidney disease, but the relationship is not the same at all stages. This finding has implications for the design of renoprotective strategies and the interpretation of clinical trials in type 1 diabetes.

Adult↗

PubMed2005

Complex relationship between blood pressure and mortality in type 2 diabetic patients: a follow-up of the Botnia Study.

The presence of hypertension aggravates the high cardiovascular risk in type 2 diabetic patients. Pulse pressure is a marker of arterial stiffness and constitutes a risk factor for cardiovascular mortality. This study examines the relationship between different blood pressure indices and mortality in a cohort of type 2 diabetic patients. A total of 1294 type 2 diabetic patients with a median age of 69.1 years participated in the Botnia Study from 1990 to 1997. In 2004, after a median follow-up of 9.5 years, data on mortality was collected from the national population registry and hospital records. Systolic and diastolic blood pressure correlated negatively with mortality after adjustment for other risk factors. The association between low systolic and diastolic blood pressure and mortality was pronounced in patients with previous cardiovascular disease. A U-shaped association between pulse pressure and mortality was observed in elderly patients. These observations could be linked to arterial stiffness and heart failure. Low blood pressure in high-risk patients is likely to be a marker of poor health rather than the cause of mortality. The results suggest that the role of blood pressure as a risk marker in elderly type 2 diabetic patients with cardiovascular disease needs to be reevaluated.

Age Factors↗

PubMed2005

Incidence of end-stage renal disease in patients with type 1 diabetes.

CONTEXT: End-stage renal disease (ESRD) is one of the most severe complications of type 1 diabetes. Yet, data on patients' risk of developing ESRD are sparse. OBJECTIVES: To estimate the long-term risk of developing ESRD and to assess how age at diagnosis of diabetes, time period of diagnosis, and sex affect the risk. DESIGN, SETTING, AND PATIENTS: A cohort of all patients younger than 30 years diagnosed as having type 1 diabetes in Finland in 1965-1999 (n = 20,005) was identified from the Finnish Diabetes Register. The cohort was followed up from diagnosis of diabetes until development of ESRD (dialysis or kidney transplantation as identified from the Finnish Registry for Kidney Diseases), death, or end of follow-up on December 31, 2001. MAIN OUTCOME MEASURE: Cumulative incidence of ESRD, accounting for death as a competing risk. RESULTS: The cohort was followed up for maximally 37 years, with a median of 16.7 years. During 346 851 person-years, 632 patients developed ESRD. The cumulative incidence of ESRD was 2.2% at 20 years and 7.8% at 30 years after diagnosis. The risk of developing ESRD was lowest in patients whose diagnosis occurred at younger than 5 years. The risk of ESRD was lower for patients diagnosed as having type 1 diabetes in later years. The risk did not differ significantly between sexes. CONCLUSIONS: With regard to ESRD, the prognosis of type 1 diabetes has improved during the past 4 decades. Children diagnosed as having diabetes before age 5 years have the most favorable prognosis. Overall, incidence of ESRD appears to be lower than previously estimated.

Adolescent↗

PubMed2005

Mechanisms of disease: Pathway-selective insulin resistance and microvascular complications of diabetes.

Resistance to the actions of insulin is strongly associated with the microvascular complications of diabetes. To the extent that insulin resistance leads to hyperglycemia, dyslipidemia and hypertension, this association is not surprising. It is now clear that insulin also has direct actions in the microvasculature that influence the development and progression of microvascular disease. In the healthy state, insulin appears to have only minor effects on vascular function, because of the activation of opposing mediators such as nitric oxide and endothelin-1. Diabetes and obesity, however, are associated with selective insulin resistance in the phosphatidylinositol-3-kinase signaling pathway, which leads to reduced synthesis of nitric oxide, impaired metabolic control and compensatory hyperinsulinemia. By contrast, insulin signaling via extracellular signal-regulated kinase dependent pathways is relatively unaffected in diabetes, tipping the balance of insulin's actions so that they favor abnormal vasoreactivity, angiogenesis, and other pathways implicated in microvascular complications and hypertension. In addition, preferential impairment of nonoxidative glucose metabolism leads to increased intracellular formation of advanced glycation end products, oxidative stress and activation of other pathogenic mediators. Despite a strong temporal association, a causal link between pathway-selective insulin resistance and microvascular damage remains to be established. It is possible that this association reflects a common genotype or phenotype. Nonetheless, insulin resistance remains an important marker of risk and a key target for intervention, because those patients who achieve a greater improvement of insulin sensitivity achieve better microvascular outcomes.

Animals↗

PubMed2005

High-throughput pedigree drawing.

Family trees have long been a valuable visual tool for geneticists in identifying clusters of inherited traits and genotypes. As more data are collected, drawing the graphs by hand becomes impractical and, for this reason, we have developed the pedigree software CraneFoot. It can process any family graph with minimal computational cost by making a pedigree transformation that enables the use of a linear node positioning algorithm. The program is designed for automated drawing to printed media and efficient visual classification of genetically interesting families from large data sets. It also incorporates a robust pedigree topology check with detailed error messages.

Algorithms↗

PubMed2005

Pulse wave reflection in currently and previously preeclamptic women.

OBJECTIVE: Disturbed maternal endothelial function is believed to be central in the pathogenesis of preeclampsia and has been observed to persist for several years following the preeclamptic pregnancy. Endothelial dysfunction has been reported to cause increased pulse wave reflection, a measure of systemic arterial stiffness. This study tested the hypothesis that preeclampsia and a history of preeclampsia are associated with increased pulse wave reflection. DESIGN AND METHODS: We carried out a cross-sectional case-control study of 26 pregnant women with preeclampsia, 26 pregnant controls, 22 normotensive nonpregnant previously preeclamptic women, and 22 nonpregnant controls. Pulse wave reflection was assessed by applanation tonometry on the radial artery. RESULTS: Pregnant preeclamptic women had a significantly higher heart rate-adjusted augmentation index than did pregnant controls (23 +/- 1 vs. 8 +/- 1%, P < 0.001). The augmentation index of women with a history of preeclampsia was similar to that of the nonpregnant controls (9 +/- 2 vs. 9 +/- 2%, P = 0.78). In a multiple linear regression analysis (R2 = 0.76) the augmentation index of pregnant women was independently associated with a diagnosis of preeclampsia (P < 0.001) and heart rate (P < 0.001), but not with mean arterial blood pressure (P = 0.59). CONCLUSIONS: This study demonstrates that pulse wave reflection and, thus, systemic arterial stiffness are increased in pregnant women with preeclampsia, but not in normotensive nonpregnant women with a history of preeclampsia. The results support the concept of generalized vascular dysfunction in preeclampsia.

Adult↗

PubMed2005

Leisure time physical activity is associated with poor glycemic control in type 1 diabetic women: the FinnDiane study.

OBJECTIVE: We studied the association between leisure time physical activity (LTPA) and glycemic control, insulin dose, and estimated glucose disposal rate (eGDR) in type 1 diabetes. RESEARCH DESIGN AND METHODS: This is a cross-sectional study of 1,030 type 1 diabetic patients participating in the Finnish Diabetic Nephropathy Study, a nationwide multicenter study. LTPA was assessed by a validated 12-month questionnaire and expressed in metabolic equivalent (MET) units. Patients were grouped as sedentary (LTPA <10 MET h/week, n = 247), moderately active (LTPA 10-40 MET h/week, n = 568), and active (LTPA >40 MET h/week, n = 215). Outcome measures were HbA(1c), insulin dose, and eGDR (estimate of insulin sensitivity based on waist-to-hip ratio, hypertension, and HbA(1c)). RESULTS: LTPA correlated with HbA(1c) in women (r = -0.12, P = 0.007) but not in men (r = -0.03, P = 0.592). Sedentary women had higher HbA(1c) than moderately active and active women: 8.8 +/- 1.4% vs. 8.3 +/- 1.4% vs. 8.3 +/- 1.4% (P = 0.004), whereas HbA(1c) in men was 8.4 +/- 1.3% vs. 8.2 +/- 1.4% vs. 8.2 +/- 1.3% (P = 0.774), respectively. In men, insulin doses were 0.74 +/- 0.21 vs. 0.71 +/- 0.20 vs. 0.68 +/- 0.23 IU . kg(-1) . 24 h(-1) (P = 0.003). In both sexes, sedentary patients had lower eGDRs than active patients [median (interquartile range) 5.5 (4.0-8.2) vs. 6.8 (4.7-8.8) vs. 6.7 (4.6-8.6) mg . kg(-1) . min(-1); P < 0.01 for sedentary vs. others]. Age, obesity, smoking, insulin dose, social class, diabetic nephropathy, or cardiovascular disease did not explain the results. CONCLUSIONS: Low levels of LTPA were associated with poor glycemic control in type 1 diabetic women. Men seem to use less insulin when physically active. Increased LTPA levels were associated with increased estimated insulin sensitivity. Longitudinal studies are needed to further clarify the effects of LTPA on type 1 diabetes.

Adult↗

PubMed2005

Serum adiponectin is increased in type 1 diabetic patients with nephropathy.

OBJECTIVE: To elucidate whether serum adiponectin is associated with renal function, low-grade inflammatory markers, metabolic control, and insulin resistance in type 1 diabetic patients with and without nephropathy. RESEARCH DESIGN AND METHODS: A total of 189 type 1 diabetic patients from the Finnish Diabetic Nephropathy Study were divided into three groups based on their urinary albumin excretion rate (AER): patients with normal AER (n = 66) had no antihypertensive medication, while patients with microalbuminuria (n = 63) or macroalbuminuria (n = 60) were all treated with an ACE inhibitor. Renal function was estimated with the Cockcroft-Gault formula. Adiponectin was measured by an in-house time-resolved immunofluorometric assay. RESULTS: Adiponectin concentrations were higher in women than in men, but since there was no significant difference in sex distribution between the groups, data were pooled. Adiponectin concentrations were higher in patients with macroalbuminuria (19.8 +/- 12.0 mg/l) than in patients with microalbuminuria (13.1 +/- 4.8 mg/l) or normoalbuminuria (11.8 +/- 4.2 mg/l). In a univariate analysis, adiponectin was positively associated with creatinine (r = 0.41; P < 0.0001), AER (r = 0.33; P < 0.0001), interleukin-6 (r = 0.22; P = 0.002), systolic blood pressure (r = 0.22; P = 0.004), HbA(1c) (r = 0.17; P = 0.02), total cholesterol (r = 0.16; P = 0.03), and HDL cholesterol (r = 0.16; P = 0.03) and negatively with estimated glomerular filtration rate (GFR; r = -0.52; P < 0.0001) and waist-to-hip ratio (WHR; r = -0.16; P = 0.03). In a multiple linear regression analysis including the above variables, estimated GFR, AER, and WHR were independently associated with adiponectin levels (r(2) = 0.32). CONCLUSIONS: Serum adiponectin concentrations are increased in type 1 diabetic patients with nephropathy, and levels are further associated with renal insufficiency.

Adiponectin↗

PubMed2005

Metabolic syndrome in type 1 diabetes: association with diabetic nephropathy and glycemic control (the FinnDiane study).

OBJECTIVE: The aim of this study was to estimate the prevalence of the metabolic syndrome in Finnish type 1 diabetic patients and to assess whether it is associated with diabetic nephropathy or poor glycemic control. RESEARCH DESIGN AND METHODS: In all, 2,415 type 1 diabetic patients (51% men, mean age 37 years, duration of diabetes 22 years) participating in the nationwide, multicenter Finnish Diabetic Nephropathy (FinnDiane) study were included. Metabolic syndrome was defined according to the National Cholesterol Education Program diagnostic criteria. Patients were classified as having normal albumin excretion rate (AER) (n = 1,261), microalbuminuria (n = 326), macroalbuminuria (n = 383), or end-stage renal disease (ESRD) (n = 164). Glycemic control was classified as good (HbA1c <7.5%), intermediate (7.5-9.0%), or poor (>9.0%). Creatinine clearance was estimated with the Cockcroft-Gault formula. RESULTS: The overall prevalence of metabolic syndrome was 38% in men and 40% in women. The prevalence was 28% in those with normal AER, 44% in microalbuminuric patients, 62% in macroalbuminuric patients, and 68% in patients with ESRD (P < 0.001). Patients with metabolic syndrome had a 3.75-fold odds ratio for diabetic nephropathy (95% CI 2.89-4.85), and all of the separate components of the syndrome were independently associated with diabetic nephropathy. The prevalence of metabolic syndrome was 31% in patients with good glycemic control, 36% in patients with intermediate glycemic control, and 51% in patients with poor glycemic control (P < 0.001). Similarly, metabolic syndrome increased with worsening creatinine clearance. CONCLUSIONS: The metabolic syndrome is a frequent finding in type 1 diabetes and increases with advanced diabetic nephropathy and worse glycemic control.

Adult↗