Päivi Tossavainen

Meta-analysis of the significance of asymptomatic bacteriuria in diabetes.

OBJECTIVE To evaluate whether asymptomatic bacteriuria (ASB) is more common in patients with diabetes than among control subjects. In addition, we wanted to clarify the clinical significance of ASB in patients with diabetes. RESEARCH DESIGN AND METHODS We conducted a systematic review and meta-analysis of published data since 1966. Twenty-two studies fulfilled the inclusion criteria of the meta-analysis. RESULTS ASB was present in 439 of 3,579 (12.2%) patients with diabetes and in 121 of 2,702 (4.5%) healthy control subjects. ASB was more common both in patients with type 1 diabetes (odds ratio 3.0 [95% CI 1.1–8.0]) and type 2 diabetes (3.2 [2.0–5.2]) than in control subjects. The point prevalence of ASB was higher in both women (14.2 vs. 5.1%; 2.6 [1.6–4.1]) and men (2.3 vs. 0.8%; 3.7 [1.3–10.2]) as well as in children and adolescents (12.9 vs. 2.7%; 5.4 [2.7–11.0]) with diabetes than in healthy control subjects. Albuminuria was more common in patients with diabetes and ASB than those without ASB (2.9 [1.7–4.8]). History of urinary tract infections was associated with ASB (1.6 [1.1–2.3]). CONCLUSIONS We were able to show that the prevalence of ASB is higher in all patients with diabetes compared with control subjects. We also found that diabetic subjects with ASB more often had albuminuria and symptomatic urinary tract infections.

Prevention and treatment of microvascular disease in childhood type 1 diabetes

INTRODUCTION The incidence of type 1 diabetes (T1D) is increasing worldwide, particularly in children, and is associated with a significant burden, mainly related to the development of vascular complications. The prevention and treatment of microvascular complications, which include nephropathy, retinopathy and neuropathy, are of paramount importance to decrease the associated mortality and morbidity. SOURCES OF DATA A literature search was performed on Medline and articles on microvascular complications, with particular emphasis on the increasing incidence of childhood T1D and its implications on prevention and treatment of complications, were selected. AREAS OF AGREEMENT The incidence of childhood T1D is increasing. Early identification of subjects at risk for long-term complications and early implementation of preventive and therapeutic strategies are fundamental in order to reduce the burden associated with microvascular complications of diabetes. Improving glycaemic control is the principle way of preventing and treating T1D complications. AREAS OF CONTROVERSY In adults with T1D and microvascular complications, treatment with anti-hypertensive drugs and statins is increasingly common, whereas there are no definitive indications for treatment with these drugs in children and adolescents with early signs of complications. GROWING POINTS There is growing interest in the development of new preventive and therapeutic strategies targeting specific pathways implicated in the pathogenesis of microvascular complications. AREAS TIMELY FOR DEVELOPING RESEARCH Investigations to clarify genetic and environmental factors implicated in the pathogenesis of microvascular complications could lead to the identification of biochemical markers with high predictive values, to be used as a guide for screening and intervention programmes.

Cardiovascular risk factors in 2011 and secular trends since 2007: The Cardiovascular Risk in Young Finns Study

Aims: Cardiovascular risk factor levels in 2011 and 4-year changes between 2007 and 2011 were examined using data collected in follow-ups of the Cardiovascular Risk in Young Finns Study. Methods: The study population comprised 2063 Finnish adults aged 34–49 years (45% male). Lipid and blood pressure levels, glucose and anthropometry were measured and life style risk factors examined with questionnaires. Results: Mean total cholesterol level in 2011 was 5.19 mmol/l, low density lipoprotein (LDL)-cholesterol 3.27 mmol/l, high density lipoprotein (HDL)-cholesterol 1.33 mmol/l, and triglycerides 1.34 mmol/l. Using American Diabetes Association criteria, Type 2 diabetes (T2D) was observed in 4.1% and prediabetes (fasting glucose 5.6–6.9 mmol/l or glycated hemoglobin 5.7–6.4%) diagnosed for 33.8% of the participants. Significant changes (P < 0.05) between 2007 and 2011 included an increase in waist circumference (3.3%) in women. In both sexes, systolic (−3.0% in women, −4.0% in men) and diastolic (−3.0% in women, −3.3% in men) blood pressure and triglycerides (−3.4% in women, −6.5% in men) decreased during follow-up. Conclusions: Previously observed favorable trends in LDL-cholesterol levels have leveled off among a sample of young and middle-aged adults in Finland. Triglyceride and blood pressure levels have decreased. Over one-third of the study population had prediabetes and may be at increased risk for T2D.

Prevalence and determinants of fatty liver in normal-weight and overweight young adults. The Cardiovascular Risk in Young Finns Study.

Abstract Background and aims. Fatty liver may have different determinants in normal-weight and in obese individuals. We measured factors associated with fatty liver in 863 normal-weight (BMI < 25) and 1135 overweight/obese (BMI ≥ 25) young and middle-aged adults (45% male, age 34–49 years) in the population-based Cardiovascular Risk in Young Finns Study. Methods and results. The prevalence of fatty liver detected with ultrasound was 29% in overweight/obese and 5% in normal-weight participants. In overweight/obese, the independent correlates were waist circumference (odds ratio for 1 standard deviation increase = 3.78), alanine transaminase (2.11), BMI (2.00), male sex (1.74), triglycerides (1.44), systolic blood pressure (1.31), fasting insulin (1.23), and physical activity (0.76). In normal weight, the independent correlates included alanine transaminase (3.05), smoking (2.56), systolic blood pressure (1.54), and alcohol intake (1.41). In normal-weight participants, the associations with fatty liver were stronger for alcohol intake and smoking, and weaker for triglycerides, than in overweight/obese participants (P for interaction < 0.05). Conclusion. Prevalence of fatty liver was 29% in overweight/obese and 5% in normal-weight adults. Differences in factors associated with fatty liver were seen between these two groups: alcohol intake and smoking were more strongly and triglycerides more weakly associated in normal-weight than in overweight/obese participants.

Effect of birth weight on life-course blood pressure levels among children born premature: the Cardiovascular Risk in Young Finns Study

Objectives: Both fetal growth restriction and prematurity have been associated with elevated blood pressure (BP). However, their combined effects on adult BP are unclear. Methods: Our analyses were based on 1756 participants in the population-based Cardiovascular Risk in Young Finns Study who had information on birth weight and gestational age, together with longitudinal data on cardiovascular risk markers from age 3–18 years in 1980 to age 34–49 years in 2011. Three groups were defined by birth data: those born at term (term); those born preterm (<37 weeks) with an appropriate birth weight (>−1 SD z score according to national sex and gestational week-stratified data) for gestational age (preterm appropriate birth weight for gestational age); and those born preterm with low birth weight (⩽−1 SD z score) for gestational age [preterm small birth weight for gestational age (SGA)]. Results: There were no differences between the three groups in BP at baseline, but at the 31-year follow-up (mean age 41 years), mean SBP in the preterm SGA group was 7.2 mmHg (95% confidence interval = 2.3–12.1 mmHg, P = 0.004) higher than the preterm appropriate birth weight for gestational age group and 7.3 mmHg (95% confidence interval = 5.2–9.4 mmHg, P < 0.0001) higher than the term group, adjusted for age and sex. In addition, preterm SGA individuals had a higher prevalence of adult hypertension compared with those born at term (36.9 vs. 25.4%; age, sex, and risk factors adjusted P = 0.006). Conclusion: These longitudinal data suggest that elevated BP levels associated with prematurity are more likely to be present in those with fetal growth restriction.

Prevalence of retinopathy in Finnish children and adolescents with type 1 diabetes: a cross-sectional population-based retrospective study

Aim A population-based study was carried out to evaluate the prevalence and risk factors of diabetic retinopathy (DR) in children with type 1 diabetes (T1D) in The Northern Osthrobothnia Hospital District, Finland. The aim was to compare the current prevalence and the risk factors with those obtained in a study performed in a similar setting 17 years earlier. Methods and patients The prevalence of DR was evaluated from fundus photographs in a cross-sectional manner in children and adolescents with T1D (n=297) living in the Northern Osthrobothnia Hospital District on 1 January 2007. Results The prevalence of DR was 7.6% (12/158) in males and 16.5% (23/139) in females in the present study and 7.3% in males and 12.9% in females in the former study. The mean age of the patients was 11.9 and 11.8 years, and the mean duration of diabetes was 4.9 and 5.0 years in the present and the former study, respectively. DR was associated with older age (p<0.001), longer duration of diabetes (p<0.001), higher glycated haemoglobin A1c (GHbA1c) (9.3% in those with DR vs 8.3% in those without DR, p=0.001, or 78 vs 67 mmol/mol, respectively) and female sex (p=0.016); in a logistic regression analysis, these factors explained 35% of DR. These risk factors are essentially the same as identified in the cohort 17 years earlier. GHbA1c levels had not significantly improved during that time. Conclusions The overall prevalence of DR among children with T1D was 11.8% (35/297) showing no decrease over the past 17 years; in girls, DR was diagnosed more often in the present than in the former study, but there was no change in the prevalence among the boys. Glycaemic control had remained unchanged.

Maternal but Not Paternal Association of Ambulatory Blood Pressure With Albumin Excretion in Young Offspring With Type 1 Diabetes

OBJECTIVE Familial predisposition to hypertension has been associated with the development of diabetic nephropathy in adults, but there are limited data in adolescents. Our aim was to assess whether parental ambulatory blood pressure (ABP) was associated with ABP and albumin excretion in young offspring with type 1 diabetes. RESEARCH DESIGN AND METHODS Twenty-four-hour ABP monitoring was performed in 509 young offspring (mean ± SD age 15.8 ± 2.3 years) with type 1 diabetes, 311 fathers, and 444 mothers. Systolic (SBP) and diastolic blood pressure (DBP) measurements during 24 h, daytime, and nighttime were calculated. Three early morning urinary albumin-to-creatinine ratios (ACRs), A1C, and anthropometric parameters were available for the offspring. RESULTS All paternal ABP parameters, except for nighttime SBP, were independently related to the offsprings ABP (24-h SBP β = 0.18, 24-h DBP β = 0.22, daytime SBP β = 0.25, daytime DBP β = 0.23, and nighttime DBP β = 0.18; all P < 0.01). Maternal 24-h DBP (β = 0.19, P = 0.004), daytime DBP (β = 0.09, P = 0.04), and nighttime SBP (β = 0.24 P = 0.001) were related to the corresponding ABP parameter in the offspring. Significant associations were found between the offsprings logACR and maternal ABP. The association with 24-h DBP (β = 0.16, P = 0.02), daytime DBP (β = 0.16 P = 0.02), and nighttime DBP (β = 0.15 P = 0.03) persisted even after adjustment for the offsprings ABP. Mothers of offspring with microalbuminuria had higher ABP than mothers of offspring without microalbuminuria (all P < 0.05). CONCLUSIONS In this cohort, parental ABP significantly influenced offspring blood pressure, therefore confirming familial influences on this trait. In addition, maternal ABP, particularly DBP, was closely related to ACR in the offspring, suggesting a dominant effect of maternal genes or an effect of the intrauterine environment on microalbuminuria risk.

Short-term administration of pegvisomant improves hepatic insulin sensitivity and reduces soleus muscle intramyocellular lipid content in young adults with type 1 diabetes.

CONTEXT Data on the metabolic effects of GH derived from studies using GH suppression by pharmacological agents may not reflect selective actions. OBJECTIVE The purpose of this study was to evaluate the effects of GH antagonism on glucose and lipid metabolism using pegvisomant, a selective GH receptor antagonist in patients with type 1 diabetes (T1D). DESIGN AND PARTICIPANTS In a randomized, placebo-controlled, crossover study, 10 young adults with T1D were evaluated at baseline and after 4 weeks of treatment with either 10 mg of pegvisomant or placebo. The assessments included an overnight euglycemic steady state followed by a hyperinsulinemic euglycemic clamp and used glucose and glycerol cold stable isotopes. OUTCOME MEASURES Hepatic and peripheral insulin sensitivity (IS), lipid turnover, and intramyocellular lipid (IMCL) were measured. RESULTS Compared with placebo, pegvisomant treatment resulted in lower IGF-I levels (P < .001). During the overnight steady state, insulin requirements for euglycemia (P = .019), insulin levels (P = .008), and glucose production rates (Ra) (P = .033) were reduced. During the clamp study, glucose infusion rates (P = .031) increased and glucose Ra (P = .015) decreased whereas glucose disposal rates were unchanged. Free fatty acid levels were similar during the steady state but were lower during the clamp (P = .040) after pegvisomant. Soleus muscle IMCL decreased after treatment (P = .024); however, no change in tibialis anterior muscle was observed. CONCLUSIONS The study demonstrates that GH antagonism in T1D results in improved hepatic insulin sensitivity. Lack of consistent changes in free fatty acid levels may suggest a direct effect of GH on IS. Unchanged peripheral IS despite reductions in IMCL indicate that GH-induced alterations in IMCL may not be causally linked to glucose metabolism.

Status and rationale of renoprotection studies in adolescents with type 1 diabetes

The incidence of childhood-onset type 1 diabetes (T1D) has significantly increased during the past decades, particularly in children diagnosed under the age of 5 yr (1). The long-term prognosis of young people diagnosed with diabetes is generally poor, and recent data from the USA have shown that, among children diagnosed at the age of 10 yr, the number of life years lost is 18.7 for boys and 19.0 for girls (2). Similar alarming data have emerged from a study from Norway, where childhood-onset T1D has been associatedwith a fourfold increase in the overall standardized mortality rate (3). Microvascular and macrovascular complications significantly contribute to the poor prognosis of children and adolescents with T1D (4, 5). Diabetic nephropathy (DN) is one of the most common microvascular complications affecting 15–40% subjects with T1D, with a peak incidence after 15to 20-yr diabetes duration (6). DN represents the leading cause of end-stage renal disease (ESRD) in developed countries and is also a major determinant of cardiovascular morbidity and mortality (6). Although advanced DN or diabetesrelated ESRD is rarely diagnosed in children and adolescents (7, 8), there is clear evidence that early structural and functional renal alterations develop soon after diagnosis, and these may be reflected by subtle increases in urinary albumin excretion during childhood, resulting in the development of microalbuminuria (MA) during puberty (9, 10).

Maternal type 1 and gestational diabetes: postnatal differences in insulin secretion in offspring at preschool age

Background:  It is well known that children born to mothers with diabetes in pregnancy are more likely to develop metabolic abnormalities in later life. Most prior studies have not differentiated between offspring of mothers with type 1 diabetes (T1DM) and gestational diabetes (GDM) or lack a control group of non‐exposed offspring.