E. R. Mathiesen

PREVALENCE OF MICROALBUMINURIA IN CHILDREN WITH TYPE 1 (INSULIN-DEPENDENT) DIABETES MELLITUS

SummaryThe prevalence of microalbuminuria was determined in children aged 7 to 18 years with Type 1 (insulin-dependent) diabetes of more than 2 years duration. All patients (n =102) attending 2 diabetes clinics were asked to collect 2 overnight timed urine samples for albumin analysis by radioimmunoassay. Complete urine collection was obtained in 97 patients (95%). Overnight urinary albumin excretion rates were also measured in 36 healthy children matched for age and sex. Nineteen of the 97 patients (20%) had microalbuminuria, i. e. overnight urinary albumin excretion rates above the upper normal level (14 μg/min) in both urine collections. Microalbuminuria was only demonstrated in patients aged ≥ 15 years, prevalence 37% (19/52 patients). Arterial blood pressure was elevated, mean 122/84±11/9mmHg, in the microalbuminuric group (19 patients) compared to the age-matched normoalbuminuric diabetic group (33 patients), mean 117/74±10/10 mm Hg,p < 0.001. The prevalence of simplex retinopathy was identical in these two groups, i. e. 25%. Glycosylated haemoglobin was slightly higher in the microalbuminuric patients,p < 0.10. Our cross-sectional study reveals a high prevalence (37%) of persistent microalbuminuria, a stage highly predictive of later development of diabetic nephropathy, in Type 1 diabetic children aged ≥ 15 years.

Increased blood pressure and erythrocyte sodium/lithium countertransport activity are not inherited in diabetic nephropathy

SummaryGenetic predisposition to essential hypertension, represented by maximal erythrocyte sodium/lithium countertransport activity, has been suggested as a marker for the risk of developing clinical nephropathy in Type 1 (insulin-dependent) diabetes mellitus. To evaluate this hypothesis we measured arterial blood pressure and maximal sodium/lithium countertransport activity of erythrocytes in 80 parents of 49 Type 1 diabetic patients with clinical nephropathy, 78 parents of 49 normoalbuminuric patients and 17 age-matched non-diabetic individuals. The two diabetic groups were carefully matched. In the two groups of parents blood pressure and cell sodium/lithium countertransport activity showed no significant differences (137/83 vs 133/81 mmHg and 0.33 vs 0.32 mmol/(1 cells x h) respectively). The proportion of parents who had died or received anti-hypertensive drugs was similar in the two groups.The patients with Type 1 diabetes had significantly higher sodium/lithium countertransport compared to the 39 non-diabetic control subjects independently of the presence or absence of nephropathy (p<0.002). However, patients with nephropathy tended to have higher sodium/lithium countertransport activity than normoalbuminuric patients (0.48 vs 0.41 mmol/(1 cells x h), p = 0.06). We conclude that genetic predispositions to essential hypertension and increased maximal erythrocyte sodium/lithium counter-transport activity do not appear to be risk markers for the development of clinical nephropathy in Type 1 diabetic patients.

Acute reduction of arterial blood pressure reduces urinary albumin excretion in Type 1 (insulin-dependent) diabetic patients with incipient nephropathy

SummaryThe effect of an acute reduction in arterial blood pressure upon kidney function was studied in 12 patients with Type 1 (insulin-dependent) diabetes and incipient nephropathy (persistent microalbuminuria). Renal function was assessed by measurement of the glomerular filtration rate (single bolus 51Cr-EDTA technique) and by the urinary albumin excretion rate (radioimmunoassay). The study was performed twice within 2 weeks, with the patients receiving a slow intravenous injection of either clonidine (225 μg) or saline (154 mmol/l) in random order. Clonidine reduced arterial blood pressure from 125/79±13/8 to 104/68±9/7 mmHg (p < 0.01), urinary albumin excretion rate from 68 (31–369) to 46 (6–200) μg/min (median and range) (p<0.01), and fractional clearance of albumin in all patients (median 29%) (p < 0.01). Glomerular filtration rate was 110±11 before and 106±13 ml/min/1.73 m2 after clonidine injection. The blood glucose concentration was 15±4mmol/l before and 14±5 mmol/l after clonidine injection. In agreement with findings in animal studies, our results suggest that microalbuminuria is to a large extent pressure-dependent, probably because of glomerular hypertension, and that autoregulation of glomerular filtration rate is normal in most patients with incipient diabetic nephropathy.

Risk of Diabetes Mellitus in Persons with and without HIV: A Danish Nationwide Population-Based Cohort Study

Objective In a nationwide, population-based cohort study we assessed the risk of diabetes mellitus (DM) in HIV-infected individuals compared with the general population, and evaluated the impact of risk factors for DM in HIV-infected individuals. Methods We identified 4,984 Danish-born HIV-infected individuals from the Danish HIV Cohort Study and a Danish born population-based age- and gender-matched comparison cohort of 19,936 individuals (study period: 1996–2009). Data on DM was obtained from the Danish National Hospital Registry and the Danish National Prescription Registry. Incidence rate ratios (IRR) and impact of risk factors including exposure to Highly Active Antiretroviral Therapy (HAART) and antiretroviral drugs were estimated by Poisson regression analyses. Results In the period 1996–1999 risk of DM was higher in HIV-infected individuals compared to the comparison cohort (adjusted IRR: 2.83; 95%CI: 1.57–5.09), both before (adjusted IRR: 2.40; 95%CI: 1.03–5.62) and after HAART initiation (adjusted IRR: 3.24; 95% CI: 1.42–7.39). In the period 1999–2010 the risk of DM in HIV-infected individuals did not differ from that of the comparison cohort (adjusted IRR: 0.90; 95% CI: 0.72–1.13), although the risk was decreased before HAART-initiation (adjusted IRR: 0.45; 95%CI: 0.21–0.96). Increasing age, BMI and the presence of lipoatrophy increased the risk of DM, as did exposure to indinavir, saquinavir, stavudine and didanosine. Conclusion Native HIV–infected individuals do not have an increased risk of developing DM compared to a native background population after year 1998. Some antiretroviral drugs, not used in modern antiretroviral treatment, seem to increase the risk of DM.

Pregnancy-induced sight-threatening diabetic retinopathy in women with Type 1 diabetes

Diabet. Med. 27, 431–435 (2010)

Hypoglycaemia during pregnancy in women with Type 1 diabetes

Diabet. Med. 29, 558–566 (2012)

Effects of indomethacin on kidney function in Type 1 (insulin-dependent) diabetic patients with nephropathy

SummaryWe investigated whether the glomerular synthesis of prostaglandins modulates the glomerular filtration rate and albumimiria in diabetic nephropathy. The urinary excretion of immunoreactive prostaglandin E2 (253pg/min) was significantly elevated in eight Type 1 (insulin-dependent) diabetic women with nephropathy as compared with nine normoalbuminuric Type 1 diabetic women (95pg/min) and 11 non-diabetic women (132 pg/min), respectively (p<0.01). Glomerular filtration rate (single bolus 51Cr-EDTA technique) and albuminuria (radioimmunoassay) were measured twice within two weeks in the eight Type 1 diabetic women with nephropathy. All eight patients were on a diabetic diet without sodium restriction. The study was performed as a randomized doubleblind trial, with the patients receiving either indomethacin (150mg/day) or placebo for three days prior to the kidney function studies. Indomethacin treatment induced a significant reduction in urinary prostaglandin E2 excretion (73%, p<0.01), glomerular filtration rate diminished from 120±18 to 106±17ml/min/1.73m2 (p<0.05), albuminuria declined from 148 to 69 μg/min (median and range) (p<0.05) and fractional clearance of albumin diminished 42% (p<0.05). Blood glucose concentrations were comparable during the placebo and indomethacin treatment, 13.4±4 versus 14.2±3 mmol/l, respectively. Our results suggest that glomerular filtration rate in early diabetic nephropathy is dependent on the enhanced glomerular synthesis of vasodilating prostaglandins.

Progression of diabetic retinopathy during pregnancy in women with type 2 diabetes

Aims/hypothesisWe studied the progression of diabetic retinopathy during pregnancy in women with type 2 diabetes.MethodsFundus photography was performed at median 10 (range 6–21) and 28 (27–37) gestational weeks in 80 of 110 (73%) consecutively referred pregnant women with type 2 diabetes. Diabetic retinopathy was classified in five stages. Progression was defined as at least one stage of deterioration of diabetic retinopathy and/or development of macular oedema on at least one eye between the two examinations. Macular oedema was defined as retinal thickening and/or hard exudates within a diameter of 1,500xa0µm in the macula area.ResultsDiabetic retinopathy, mainly mild, was present in 11 (14%) women in early pregnancy. Median duration of diabetes was 3xa0years (range 0–16xa0years). At baseline, HbA1c was 6.4% (1.0) (mean [SD]), systolic BP 121 (13) and diastolic BP 72 (9) mmHg. Prior to pregnancy, 22 (28%) women had been on insulin treatment. During pregnancy 74 women (93%) were treated with insulin and 11 (14%) with antihypertensive medication. Progression of diabetic retinopathy was observed in 11 (14%) women. Progression was mainly mild, but one woman with poor glycaemic control and uncontrolled hypertension progressed from mild retinopathy to sight-threatening retinopathy with proliferations, clinically significant macular oedema and impaired vision in both eyes. Progression of diabetic retinopathy was associated with a longer duration of diabetes (pu2009=u20090.03) and insulin treatment before pregnancy (pu2009=u20090.004).Conclusions/interpretationDespite a low risk of progression of retinopathy in pregnant women with type 2 diabetes, sight-threatening deterioration did occur.

Reduced prevalence of early preterm delivery in women with Type 1 diabetes and microalbuminuria—possible effect of early antihypertensive treatment during pregnancy

Aimsu2002 In normotensive women with Type 1 diabetes and microalbuminuria we previously found preterm delivery (< 34 weeks) in 23% of the pregnancies. Antihypertensive treatment was initiated in late pregnancy when preeclampsia was diagnosed and diastolic blood pressure > 90 mmHg. From April 2000 our routine was changed and early antihypertensive treatment with methyldopa was initiated if antihypertensive treatment was given prior to pregnancy, if urinary albumin excretion (UAE) was > 2 g/24 h, or blood pressure > 140/90 mmHg. The present study describes the impact of this more aggressive antiypertensive treatment in the prevalence of preterm delivery.

Stillbirth in diabetic pregnancies

Pregnancy in women with pregestational diabetes is associated with high perinatal morbidity and mortality. Stillbirth accounts for the majority of cases with perinatal death. Intrauterine growth restriction, pre-eclampsia, foetal hypoxia and congenital malformations may be contributing factors, but more than 50% of stillbirths are unexplained. Majority of stillbirths are characterised by suboptimal glycaemic control during pregnancy. Foetal hypoxia and cardiac dysfunction secondary to poor glycaemic control are probably the most important pathogenic factors in stillbirths among pregnant diabetic women. There is thus a need for new strategies for improving glycaemic control to near-normal levels throughout pregnancy and for preventing and treating hypertensive disorders in pregnancy. Antenatal surveillance tests including ultrasound examinations of the foetal growth rate, kick counting and non-stress testing of foetal cardiac function are widely used. However, future research should establish better antenatal surveillance tests to identify the infants susceptible to stillbirth before it happens.