Frequent pain in older people with and without diabetes - Finnish community based study.

BACKGROUND: The association between pain and diabetes in older people has been largely unexplored. The aim of this survey was to analyze the prevalence and characteristics of pain among Finnish men and women 65 or older with and without diabetes in primary care. METHODS: All home-dwelling persons 65 years or older with diabetes (N = 527) and age and gender matched controls (N = 890) were identified from electronic patient records. Frequent pain was regarded as any pain experienced more often than once a week, and it was divided into pain experienced several times a week but not daily and pain experienced daily or continuously. The Numeric Rating Scale (0-10) (NRS) was used to assess the intensity and interference of the pain. RESULTS: The number of subjects who returned the questionnaire was 1084 (76.5%). The prevalence of frequent pain in the preceding week was 50% among women without diabetes and 63% among women with diabetes (adjusted, p = 0.22). In men, the corresponding proportions were 42% without diabetes and 47% with diabetes (adjusted, p = 0.58). In both genders, depressive symptoms and the number of comorbidities were associated with pain experienced more often than once a week and with daily pain. Diabetes was not associated with pain intensity or pain interference in either women or men. CONCLUSIONS: Pain in older adults is associated with depressive symptoms and the number of comorbidities more than with diabetes itself.

The association of adiponectin and low-grade inflammation with the course of metabolic syndrome.

BACKGROUND AND AIMS: Metabolic syndrome (MetS) is associated with low-grade inflammation. The connections of adiponectin and inflammatory cytokines with the course of MetS are not well-known. The aim of this study was to investigate the relation of adiponectin and low-grade inflammation with the development or resolution of MetS. METHODS AND RESULTS: In the town of Pieksämäki, Finland, five complete age groups (n = 1.294) were invited for health check-ups in 1997-1998 for the first time and in 2003-2004 for the second time. The final study population included 284 men and 396 women. MetS was defined according to the National Cholesterol Education Program criteria in the beginning and at the end of the 6-year research period, and adiponectin, high-sensitivity C-reactive protein (hs-CRP), interleukin-1 receptor antagonist (IL-1Ra) and interleukin-1 beta (IL-1ß) levels were determined from baseline samples. Both male and female study subjects were divided into four groups according to the diagnosis of MetS in the two check-ups: not diagnosed at either check-up (No MetS), diagnosed only at the second check-up (Incident MetS), diagnosed only at the first check-up (Resolute MetS), and diagnosed at both check-ups (Persistent MetS). Baseline adiponectin, IL-1Ra and IL-1ß levels and IL-1ß/IL-1Ra -ratio were found to predict Incident MetS, when adjusted for the change in BMI, age, smoking status and physical activity. Our data also suggested that a high adiponectin level and low hs-CRP and IL-1Ra levels predict the resolution of MetS. CONCLUSION: Adiponectin and inflammatory markers can predict the course of MetS.

Ageing and associations of fasting plasma glucose and 2 h plasma glucose with HbA(1C) in apparently healthy population. "FIN-D2D" study.

OBJECTIVE: In this FIN-D2D cross-sectional survey the relationship of age with HbA(1c) and fasting and 2h glucose in the oral glucose tolerance test (OGTT) was explored in apparently randomly selected healthy population. PATIENTS AND METHODS: The glycaemic parameters were measured in 1344 men and 1482 women (aged 45-74 years), and among them we excluded all subjects with known diabetes, hypertension or dyslipidaemia. The final analyses for HbA(1c) and the ratios of fasting glucose/HbA(1c) and 2h glucose/HbA(1c) included 649 men and 804 women. RESULTS: Mean age was 57 years and BMI 26.1kg/m(2) for both genders. HbA(1c) increased in both genders with age (p<0.001). For a particular fasting glucose level HbA(1c) level was higher in older age groups (p<0.001 for linearity). By contrast, a particular 2h plasma glucose value in OGTT implied significantly lower HbA(1c) in the elderly (p<0.001 for linearity). CONCLUSION: In apparently healthy population, screened with OGTT, in older individuals compared with younger ones a particular HbA(1c) value implies slightly lower fasting glucose, but relatively higher 2h glucose. These results need to be verified in different populations. The effects of age on relation between HbA(1c) and plasma glucose should be taken into account in classifying people into different dysglycaemia categories.

Serum calcium level is associated with metabolic syndrome in the general population: FIN-D2D study.

BACKGROUND: The aim of this cross-sectional study was to examine the association between serum calcium and the components of metabolic syndrome (MetS). METHODS: As a part of the national prevention program of diabetes in Finland (FIN-D2D), a randomly selected study population of 4500 middle-aged men and women were recruited from three central hospital district areas. Anthropometric measurements were performed by a trained nurse. An oral glucose tolerance test was performed and serum calcium and lipids were measured. We assessed current medications, physical activity, smoking, alcohol consumption, calcium intake, and vitamin D intake. The MetS was defined according to the criteria of the updated National Education Program. The study population consisted of 2896 individuals: 1396 men (62% of invited individuals) and 1500 women (66.7% of invited individuals). RESULTS: The mean age was 60.3±8.3 years in men and 59.8±8.5 years in women. The prevalence of MetS was 50.7% in women and 55.8% in men. The prevalence of MetS and its components, except high-density lipoprotein (HDL)-cholesterol, increased linearly with increasing serum calcium (P<0.001), even after adjustment for age, physical activity, alcohol, vitamin D intake, calcium intake, and smoking. The threshold value for serum calcium for MetS was 2.50 mmol/l in this population. The association of MetS with total serum calcium was similar even after exclusion of patients treated with hypertensive drugs. The drug treatments for hypertension, dyslipidemia, and diabetes increased in a similar pattern. CONCLUSIONS: Serum calcium level is associated with MetS and its components, except HDL-cholesterol.

Nateglinide combination therapy with basal insulin and metformin in patients with Type 2 diabetes.

AIMS: To compare the effect of adding nateglinide or placebo on postprandial glucose excursions (PPGEs), glycated haemoglobin (HbA(1c)), diurnal glucose profiles and hypoglycaemia in patients with Type 2 diabetes treated with the combination of basal insulin and metformin. RESEARCH DESIGN AND METHODS: This was an investigator-initiated, double-blind, randomized, parallel-group, study in five centres. Patients with Type 2 diabetes (n = 88, age 56.0 +/- 0.9 years, duration of diabetes 9.4 +/- 0.5 years, HbA(1c) 7.8 +/- 0.1%, body mass index 32.4 +/- 0.5 kg/m(2)) treated with basal insulin and metformin entered a 24-week period, during which basal insulin was titrated to optimize glucose control. Thereafter, the patients were randomized to receive either nateglinide (120 mg three times daily) or placebo before their main meals for 24 weeks. RESULTS: During the optimization period, HbA(1c) decreased by -0.3 +/- 0.1 and -0.4 +/- 0.2% (NS) and insulin doses increased by 10.0 IU (2.0-32.0) [0.09 IU/kg (0.02-0.34)] and 10.0 IU (0.0-19.0) [0.11 IU/kg (0.0-0.25)] (NS) in the nateglinide and placebo groups. Mean postprandial glucose during weeks 20-24 averaged 9.0 +/- 0.3 and 10.0 +/- 0.3 mmol/l in the nateglinide and placebo groups (P = 0.025) and mean PPGE averaged 2.4 +/- 0.2 and 3.1 +/- 0.2 mmol/l, respectively (P = 0.019). At 24 weeks as compared with 0 weeks, mean HbA(1c) had decreased by 0.41 +/- 0.12% in the nateglinide group and by 0.04 +/- 0.12% in the placebo group (P = 0.023). The frequency of confirmed, symptomatic hypoglycaemia was 7.7 episodes/patient-year vs. 4.7 episodes/patient-year in the nateglinide and placebo groups (P = 0.031). CONCLUSIONS: Addition of a short-acting insulin secretagogue at main meals improves postprandial hyperglycaemia during combination therapy with basal insulin and metformin, but increases the frequency of hypolycaemia.

Levels of adiponectin, C-reactive protein and interleukin-1 receptor antagonist are associated with insulin sensitivity: a population-based study.

BACKGROUND: We evaluated the relationship of insulin sensitivity (assessed with the quantitative insulin sensitivity check index, QUICKI) to adiponectin and pro-inflammatory markers, levels of high-sensitivity C-reactive protein (hs-CRP) and interleukin-1 receptor antagonist (IL-1 Ra). METHODS: Cross-sectional study. Study population (N=923, i.e 411 men and 512 women) included five different population-based age groups (born in 1942, 1947, 1952, 1957 and 1962), [mean age 46 years and mean body mass index (BMI) 26 kg/m(2)]. Study protocol included an interview and measurements of anthropometric parameters and glucose, insulin, adiponectin, hs-CRP and IL-1 Ra. RESULTS: Correlation (r) between QUICKI and adiponectin level was 0.334 [95% confidence intervals (CI), 0.275-0.392] and partial correlation adjusted for gender, BMI, smoking status, physical activity and age was 0.247 (95% CI, 0.185-0.308). There was negative correlation between QUICKI and IL-1 Ra (r= -0.385; 95% CI, -0.440 to -0.328) which remained statistically significant after the adjustment for confounding factors (r= -0.178; 95% CI, -0.240 to -0.113). Similarly, QUICKI was negatively correlated with hs-CRP (r= -0.241; 95% CI, -0.302 to -0.178), but after the adjustment it lost its statistical significance. There was a statistically significant gender difference (p=0.018) in correlation between QUICKI and IL-1 Ra levels (men: r= -0.348; 95% CI, -0.436 to - 0.261; women r= -0.500; 95% CI, -0.537 to -0.398). CONCLUSIONS: Our results show that adiponectin level and markers of low-grade inflammation are related to insulin sensitivity. Adiponectin and IL-1 Ra levels might be better markers of the risk of obesity and type 2 diabetes than hs-CRP.

Gender differences in C-reactive protein, interleukin-1 receptor antagonist and adiponectin levels in the metabolic syndrome: a population-based study.

AIMS: We explored gender differences in the association of high-sensitivity C-reactive protein (hs-CRP), interleukin-1 receptor antagonist (IL-1Ra) and adiponectin with the metabolic syndrome (MetS) defined by the National Cholesterol Education Program (NCEP) and the International Diabetes Federation (IDF) criteria. METHODS: A population-based study of 923 middle-aged subjects in Pieksämäki, East Finland. RESULTS: The prevalence of the MetS according to the IDF and NCEP definitions was 38% and 34% in men (N = 405) and 34% and 27% in women (N = 497), respectively. hs-CRP and IL-1Ra levels were higher in subjects with the MetS compared with those without the MetS in both sexes (P < 0.001). The levels of hs-CRP (P < 0.001) and IL-1Ra (P = 0.0016 for NCEP criteria, P = 0.0028 for IDF criteria) were significantly higher in women with MetS than in men with MetS. In contrast, in subjects without MetS, no gender differences in the levels of hs-CRP or IL-1Ra were found. CONCLUSION: Women with MetS, defined by the IDF or NCEP criteria, had higher levels of hs-CRP and IL-1Ra than did men with MetS. Thus, low-grade inflammation may contribute to the high risk of cardiovascular disease in women with MetS.

Sleep-disordered breathing is related to an increased risk for type 2 diabetes in middle-aged men, but not in women--the FIN-D2D survey.

AIM: To determine the association between sleep-disordered breathing (SDB) and obesity, diabetes and glucose intolerance among middle-aged men and women in Finland. METHODS: A multicentre, population-based, cross-sectional survey in Finland. A total of 1396 men and 1500 women aged 45-74 years participated in the survey between 2004 and 2005. The study subjects underwent a health examination including an oral glucose tolerance test and filled a questionnaire describing their sleep habits. RESULTS: Middle-aged men with SDB had an increased prevalence of diabetes and abnormal glucose tolerance. These associations were not found among middle-aged women. After adjustments for age, body mass index, smoking and central nervous system-affecting medication, SDB was independently associated with diabetes and glucose intolerance in men, but not in women. CONCLUSION: Middle-aged men with SDB have an independent risk of type 2 diabetes. However, both diabetes and SDB exhibit a strong association with obesity and especially with central obesity, reflecting increased visceral fat. In clinical practice especially male patients with diabetes should always be asked about habitual snoring and about possible sleep apnoea.

Plasma endothelin in postmenopausal women with type 2 diabetes mellitus and metabolic syndrome: a comparison of oral combined and transdermal oestrogen-only replacement therapy.

AIM: Type 2 diabetes and metabolic syndrome are major cardiovascular risk factors in postmenopausal women, but the role of vasoconstrictive endothelin-1 (ET-1) in these conditions is not known. We studied the levels of ET-1 and the effect of postmenopausal hormonal therapy on ET-1 levels in postmenopausal women. METHODS: We compared plasma levels of ET-1 in 22 postmenopausal type 2 diabetic women and 14 postmenopausal women with metabolic syndrome with plasma levels in 10 healthy postmenopausal control women. The basal values for ET-1 were measured for all groups. These women were then randomised to receive in a double-dummy, crossover trial: either oral continuous oestradiol (2.0 mg) + norethisterone acetate (1.0 mg) per day or continuous transdermal oestrogen-only (50 mg/day) for 3 months. Between the active therapy there were 3-month wash-out periods. ET-1-values were measured again at the end of each treatment period. RESULTS: The type 2 diabetic women had significantly (p < 0.003) elevated ET-1 levels (4.8+/-1.0 pg/ml) whereas those with metabolic syndrome (4.4+/-1.7 pg/ml]) had non-significantly (NS) elevated ET-1 levels compared to controls (3.6+/-0.3 pg/ml). Both oral and transdermal hormone replacement therapy (HRT) failed to affect plasma ET-1 except in 14 hypertensive women from the diabetes and metabolic syndrome groups who were on angiotensin convertase enzyme (ACE) inhibitors. These women's ET-1 levels before oral HRT (4.6+/-1.1 pg/ml) fell to 4.1+/-0.9 pg/ml (p < 0.05). CONCLUSIONS: Type 2 diabetes in postmenopausal women is associated with elevated ET-1 levels. Oestrogen replacement therapy does not affect the levels of ET-1 in postmenopausal women with type 2 diabetes or metabolic syndrome.

Single-nucleotide polymorphisms may cause erroneous results in primer-introduced restriction enzyme analyses: a case of molecular misdiagnosis of homozygous vs heterozygous familial hypercholesterolemia.

PCR amplification followed by a primer introduced restriction analysis PCR (PIRA-PCR) is a widely used method to detect point mutations. Usually the artificial RFLP is created by siting one nucleotide mismatch near the 3; end of the primer. This does not alter the hybrization of the primer to the target DNA sequence. Unfortunately, unexpected single nucleotide polymorphisms (SNPs) may lead to additional mismatches and result in no amplification of the allele having unexpected SNP. We describe a warning example in which heterozygous familial hypercholesterolemia patient had an unexpected SNP and this led to his misdiagnosis.

Troglitazone reduces hyperglycaemia and selectively acute-phase serum proteins in patients with Type II diabetes.

AIMS/HYPOTHESIS: Inflammation could play a part in insulin resistance. Thiazolidinediones, new antidiabetic drugs, possess anti-inflammatory effects in vitro. We investigated if acute-phase serum proteins are increased in patients with Type II (non-insulin-dependent) diabetes mellitus who had been treated with insulin and whether troglitazone has anti-inflammatory effects in vivo. METHODS: A total of 27 patients (age 63.0+/-1.7 years, HbA1c 8.8+/-0.3%, BMI 32.7+/-0.8 kg/m2, duration 15.2+/-1.4 years, insulin dose 73.3+/-7.0 U/day) participated in the study. The patients received daily either 400 mg troglitazone or placebo for 16 weeks. Blood samples were taken at baseline, at the end of therapy and after a follow-up time of 23+/-4 days. RESULTS: The concentrations of serum amyloid A (6.2+/-1.1 mg/l) and C-reactive protein (6.1+/-1.1 mg/l) were increased (p < 0.001) and complement protein C3 (1.69+/-0.05 g/l) was also above the reference range for healthy subjects. Placebo treatment had no effect on glucose or inflammation, whereas troglitazone reduced fasting glucose (from 10.4+/-0.6 mmol/l to 8.1+/-0.5 mmol/l, p < 0.01), HbA1c (from 8.7+/-0.3% to 7.5+/-0.3%, p < 0.01), insulin requirements (from 75+/-10 U/day to 63+/-10 U/day, p < 0.05), serum amyloid A (from 6.3+/-1.5 mg/l to 4.0+/-1.3 mg/l, p = 0.001), alpha-1-acid glycoprotein (from 906+/-51 mg/l to 729+/-52 mg/l, p = 0.001) and C3 (from 1.72+/-0.07 g/l to 1.66+/-0.06 g/l, p < 0.05) but not alpha-1-antitrypsin, ceruloplasmin, C-reactive protein or haptoglobin significantly. Concentrations of glucose and acute-phase reactants had returned to those before treatment at the follow-up visit. CONCLUSION/INTERPRETATION: In Type II diabetic patients serum amyloid A and complement protein C3 are raised. Troglitazone exerts a selective reversible action on some acute-phase proteins and C3 but not on others in conjunction with the improvement in glucose metabolism.

Treatment of hypercholesterolemia and combined hyperlipidemia with simvastatin and gemfibrozil in patients with NIDDM. A multicenter comparison study.

OBJECTIVE: To compare the lipid-lowering efficacies of simvastatin and gemfibrozil in NIDDM patients with combined (mixed) hyperlipidemia (CHL) or isolated hypercholesterolemia (IHC). RESEARCH DESIGN AND METHODS: Patients with primary dyslipidemia and NIDDM were recruited for this double-blind, double-dummy comparison study from 10 Finnish centers. After a 4-week placebo run-in period, they were randomly assigned to simvastatin or gemfibrozil. The simvastatin group (n = 47) received 10 mg once nightly for 8 weeks, 20 mg for the next 8 weeks, and 40 mg for the third 8-week period. The gemfibrozil group (n = 49) received 600 mg twice daily throughout the 24 weeks. The lipid-lowering efficacies of both drugs were compared in all patients as well as separately in patients with CHL and IHC. RESULTS: In all patients, simvastatin reduced LDL and total cholesterol and the LDL-to-HDL cholesterol ratio more effectively, whereas gemfibrozil was more effective in elevating HDL cholesterol and decreasing triglyceride levels. The drug effects differed according to lipid phenotype at baseline. Simvastatin decreased LDL cholesterol levels by 30-40% in both phenotypes. Gemfibrozil caused a 15% reduction in LDL cholesterol in IHC but no change in CHL patients. Simvastatin produced 15-30% reductions in triglyceride levels in CHL but no change in IHC patients. Gemfibrozil caused reductions in triglycerides in CHL (50% and more) and in IHC (40%) patients, with 12-18% increases in HDL cholesterol in these groups. CONCLUSIONS: Simvastatin is useful in both CHL and IHC patients, whereas gemfibrozil can be used in patients with high triglyceride and low or normal LDL cholesterol levels.

Complications of nephropathia epidemica: three cases.

Haemorrhagic fever with renal syndrome (HFRS) in Scandinavia is called nephropathia epidemica (NE), and is caused by the Puumala-virus, which belongs to the Hanta-virus genus. The clinical course of NE is mostly benign, complications are uncommon, and deaths are rarely observed. We report the cases of three patients who developed serious complications in the course of NE caused by the Puumala-virus. One patient died within 24 h after admission, another developed progressive neuromuscular dysfunction (Guillain-Barré syndrome) which required auxiliary ventilation for several weeks before a slow recovery, and a third patient developed empty sella syndrome with pituitary gland insufficiency. In the first two cases the diagnosis of NE was confirmed by a rapid avidity assay for IgG antibody against Puumala-virus. In the third case the clinical course, and demonstration of NE immunity 16 years later, suggested that NE might have caused the hypopituitarism. Some patients with NE caused by the Puumala-virus may require intensive-care treatment, and the development of late complications such as empty sella syndrome and hypopituitarism should be taken into consideration.