Reproducibility of erythrocyte sodium-lithium countertransport activity and ambulatory blood pressure measurements in type 1 diabetes mellitus

We aimed to study the reproducibility of sodium-lithium countertransport [SLCT] activity and ambulatory blood pressure monitoring [ABPM] in type 1 diabetes. We did this by performing repeated measurements of SLCT activity and ABPM in 11 recent-onset diabetic children and in 11 patients with longer duration of diabetes. Both parameters were related to microalbuminuria. In the older group of diabetic children a significant correlation [r = 0.78; P<0.005] in SLCT activity between the first and second study was observed [514.3±186.4 vs 491.0 ± 148.0 μmol/l erythrocytes/h]. Diurnal systolic and diastolic blood pressure were comparable at both time points within the same group of diabetic children [in group 1: 102.6±6.1 vs 108.6±7.6 mmHg N.S.; in group 2: 113.4 ± 10.6 vs 114.0±7.8 mmHg N.S. Diastolic blood pressure in group 1: 57.4±4.8 vs 65.7±6.9 mmHg N.S., in group 2: 70.6±9.1 vs 68.5±5.3 mmHg N.S.]. Moreover, there was a significant correlation in both diurnal and nocturnal systolic blood pressure between the first and second study in the whole diabetic population. Both SLCT activity and blood pressure values obtained by ABPM were found to be reproducible individual characteristic markers in type 1 diabetic children. Received: 22 November 1997 / Accepted in revised form: 30 April 1998     

Lipid lowering therapy leads to a reduction in sodium-lithium countertransport activity.

Erythrocyte sodium-lithium countertransport (SLC) was measured in 17 patients with either combined hyperlipidaemia or hypercholesterolaemia before and after lipid lowering therapy. Before treatment SLC related to the serum triglyceride level and was increased in combined hyperlipidaemia. After treatment the SLC had returned to normal and the change in SLC was related to the change in serum triglyceride levels. Raised SLC is associated with essential hypertension but is not related to blood pressure. Therefore, the association of raised SLC with hyperlipidaemia and essential hypertension appears to have different underlying mechanisms.     

Correlations between measures of insulin sensitivity and weight loss

OBJECTIVE: Many formulas have been proposed to calculate insulin sensitivity and studies have shown their effectiveness. However, few studies have been done to compare formulas. METHODS: Seventy-two obese participants completed a randomized weight loss study. Weight loss, change in body fat and change in waist circumference were used as surrogates for change in insulin sensitivity. Correlation coefficients were calculated for each of these surrogates with proposed formulas for insulin sensitivity found in the literature. RESULTS: The change in insulin sensitivity using the formula proposed by McAuley (exp(2.63-0.28 x ln(fasting insulin)-0.31 x ln(fasting triglyceride in mmol/l)) showed the greatest correlation with weight loss (r=-0.59, p<0.0001) and was statistically superior to change in fasting glucose, fasting insulin and homeostasis model assessment (HOMA). CONCLUSIONS: The insulin sensitivity formula proposed by McAuley provides an accurate means of detecting insulin resistance. As it does not require a glucose tolerance test, it is also easier and less expensive than most other formulas. Use of this formula rather than fasting glucose would detect many more patients with insulin resistance who are at risk for subsequent diabetes and other complications.     

The relationship of urinary albumin excretion rate to ambulatory blood pressure and erythrocyte sodium-lithium countertransport in NIDDM

Summary Increased erythrocyte sodium-lithium countertransport rate is found in non-diabetic subjects with essential hypertension, and in insulin-dependent diabetic subjects with nephropathy. However, relationships between these variables in non-insulin-dependent diabetic subjects are ill-defined. In order to characterise the relationships between blood pressure, urinary albumin excretion, and erythrocyte sodium-lithium countertransport, 66 subjects with non-insulin-dependent diabetes were studied. Urinary albumin excretion rate correlated with mean 24-h ambulatory systolic blood pressure (r=0.57; p<0.001), but not with sodium-lithium countertransport (r=0.06; p=0.31). No significant relationship was observed between 24-h systolic blood pressure and erythrocyte sodium-lithium countertransport (r = 0.16; p=0.17). The principal differences between microalbuminuric and normoalbuminuric subjects (albumin excretion rate >15 g·min^–1 [n=20], and <15 g·min^–1, [n=46]) were: higher 24-h systolic blood pressure (145.9 [16.8] mm Hg vs 131.9 [16.8] mm Hg; p=0.006), nocturnal heart rate (72.4 [8.9] vs 67.4 [8.9] beats·min^–1; p=0.042), and HbA₁ (11.3 [1.5]% vs 10.1 [2.0]%; p=0.028), and a longer median duration of diabetes (10.0 vs 5.0 years; p = 0.02). In contrast, there was no significant difference in sodium-lithium countertransport rate between microalbuminuric (0.41 [0.18] mmol·l^–1·h^–1) and normoalbuminuric subjects (0.39 [0.15] mmol·l^–1· h^–1; p=0.687). In multiple regression analysis controlling for race, age, body mass index and HbA₁, the significant determinants of albumin excretion rate were 24-h systolic blood pressure (B [regression coefficient]=0.029, SE[B] [standard error of B]=0.009, t=2.95, p=0.005), duration of diabetes (B=0.430, SE[B]=0.169, t=2.54, p=0.016) and male gender (B=–1.170, SE[B]=0.457, t=–2.56, p=0.015). In conclusion, albumin excretion rates in non-insulin-dependent diabetic subjects are linked to hypertension and glycaemic exposure, but show no relationship to erythrocyte sodium-lithium countertransport.Abbreviations IDDM Insulin-dependent diabetes mellitus - NIDDM non-insulin dependent diabetes mellitus - SLC sodium lithium countertransport - AER albumin excretion rate - B regression - SE coefficient; standard error of B     

Cross-sectional and longitudinal relationship of sodium-lithium countertransport to insulin, obesity and blood pressure in healthy perimenopausal women.

The objectives of this study were to assess the possible role of insulin as a regulator of red blood cell sodium-lithium countertransport and to examine the relationship of countertransport activity to change over time in insulin, blood pressure, and other variables. At baseline, countertransport was measured, and at baseline and after 2-3 years of follow-up, blood pressure, body mass index (BMI), lipids, fasting and two-hour plasma insulin and glucose were measured in 144 white healthy, premenopausal women, age 42-50 years. At baseline, using high and low categories of fasting insulin, triglycerides and BMI, countertransport was independently related to fasting insulin (P = 0.017), and triglycerides (P = 0.001), but not to BMI by analysis of variance. In similar analyses with fasting insulin, BMI, and countertransport, diastolic blood pressure was independently related only to countertransport (P = 0.003). Among the 73 who remained premenopausal after 2-3 year follow-up, baseline countertransport was significantly correlated with increases in fasting and two-hour insulin (r = 0.37, 0.38, P = 0.003, respectively), and these relationships remained significant after adjustment for change in BMI. Among subjects with high baseline countertransport, systolic blood pressure increased 5.6 mmHg compared with -2.2 mmHg with low countertransport, P = 0.001 after adjusting for baseline and change in BMI, triglycerides, and fasting and two-hour insulin. The data are consistent with a role for insulin and lipids in the regulation of sodium transport which may, in turn, play a role in blood pressure regulation. A relatively short follow-up in this healthy population suggests a relationship of baseline countertransport to changes in insulin metabolism, and blood pressure.     

A prospective study of sodium-lithium countertransport and hypertension in Utah

A 7-year prospective study of a cohort of 1,458 normotensive adults from Utah pedigrees, screened from 1980 to 1985, was done to determine whether baseline levels of sodium-lithium countertransport were associated with an increased risk of future hypertension. Subsequent new hypertension (n = 39) was ascertained in 1989 from detailed follow-up medical questionnaires (67% response). Previous segregation analyses on a subset of these pedigree members who responded (n = 342) using family relationships in addition to countertransport levels have shown statistically inferred major gene segregation of sodium-lithium countertransport levels. In the normotensive adults inferred by segregation analysis to carry the recessive major gene for high sodium-lithium countertransport, new-onset hypertension occurred in 18.8% (3 of 16) compared with 3.7% (12 of 326) in the low sodium-lithium countertransport genotype group (relative risk, 4.6 [1.6, 13.9]; p = 0.03). However, an elevated baseline sodium-lithium countertransport level without genotype information from segregation analysis did not increase the risk of future hypertension in the complete cohort of adult pedigree members (relative risk, 1.02 [0.85, 1.22]). Adjustment for other risk factors reduced the relative risk to 0.90 (0.72, 1.11). We conclude that the presence of a major gene for sodium-lithium countertransport or another closely linked gene, rather than the actual level of sodium-lithium countertransport, may increase the risk of hypertension onset. High sodium-lithium countertransport levels do not increase the risk of future hypertension for individuals in whom only polygenic and environmental effects determine sodium-lithium countertransport level.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of weight loss on insulin sensitivity and arterial stiffness in overweight adults

Obesity is characterized by metabolic and vascular abnormalities. We examined the effects of weight loss on insulin sensitivity and arterial stiffness in overweight adults. Twelve (9 females; 3 males) overweight (body mass index, 30.3 +/- 3.7) adults (54.9 +/- 3.9 years) without diabetes or vascular disease were counseled by a registered dietician to lose weight over 6 months. Vascular structure, function, and wall mechanical properties were measured via ultrasound. Intravenous glucose tolerance test, 24-hour blood pressure, body composition (dual-energy x-ray absorptiometry), and lipids were also assessed. There were significant reductions in body mass (86.3 +/- 14.2 vs 79.5 +/- 13.8 kg, P < .0001) and percentage of fat (44.3% +/- 7.0% vs 41.0% +/- 8.5%, P < .01) after weight loss. There were significant improvements in total cholesterol (6.0 +/- 0.9 vs 5.0 +/- 0.8 mmol/L, P < .0001), low-density lipoprotein cholesterol (3.9 +/- 0.7 vs 3.2 +/- 0.6 mmol/L, P < .0001), triglycerides (3.4 +/- 2.3 vs 2.4 +/- 0.9 mmol/L, P < .05), and insulin sensitivity (3.3 +/- 1.7 vs 5.4 +/- 1.6 microU x 10(-4) min(-1) mL(-1), P < .0001) after weight loss. Brachial artery compliance (P < .05) and distensibility (P < .05) curves over the physiologic pressure range improved, whereas endothelial function and intima-media thickness remained unchanged. In overweight adults, 6 months of weight loss resulted in improvements in body composition, insulin sensitivity, lipid profile, and brachial artery compliance and distensibility.     

Elevated sodium-lithium countertransport activity in erythrocytes is predictive of the development of microalbuminuria in IDDM

Summary Pathogenetic mechanisms other than the quality of metabolic control may play a role in the development of diabetic nephropathy. Some cross-sectional studies have shown that elevated erythrocyte sodium-lithium countertransport (Na ⁺ /Li ⁺ CT) activity may be linked to incipient or overt nephropathy in insulin-dependent diabetic (IDDM) patients. The aim of the present work was to ascertain if high erythrocyte Na ⁺ /Li ⁺ CT activity anticipates the development of microalbuminuria in IDDM patients. Evaluation of this cation transport system was carried out in 159 normotensive, normoalbuminuric IDDM patients, who were divided into two groups: those with values above (Group A) and those with values below (Group B) the median level in the overall population (300 μmol/erythrocytes × h). A total of 79 patients in Group A and 80 in Group B underwent periodic examinations over a similar time period (5.2 years, range 3.3–7.4 years and 5.4 years, range 3.4–7.5 years, respectively). Median sodium-lithium countertransport activity was stable when evaluated after 2 and 4 years of follow-up. Only seven patients were excluded from the protocol because changes in their sodium-lithium countertransport activity placed them on the other side of the median value with respect to their baseline measurement. Thus, 152 patients completed the study (76 in Group A and 76 in Group B). Of the 76 patients in Group A, 17 developed persistent microalbuminuria (22.3 %). The number of patients in Group B showing persistent microalbuminuria was significantly lower (4 of 76; 5.2 %; p < 0.01). The sensitivity of erythrocyte Na ⁺ /Li ⁺ CT in predicting the development of microalbuminuria was 85 % and its specificity was 55 %. Seven patients of Group A and five of Group B developed arterial hypertension. Subjects in Group A had significantly higher mean HbA_{1 c} values of twice yearly measurements than those in Group B (9.6 ± 1.7 vs 8.3 ± 1.7 %, p < 0.002, mean ± SD) despite similar daily insulin requirements. Systolic and diastolic blood pressure levels were also evaluated every 6 months and were significantly higher in the Group A than in the Group B patients, although on average within the normal range. The odds ratio for developing persistent microalbuminuria in IDDM with elevated baseline erythrocyte Na ⁺ /Li ⁺ CT activity after adjustment for gender and baseline albumin excretion rate, and mean 6 monthly plasma creatinine, HbA_{1 c} and systolic and diastolic blood pressure levels was 4.2 (95 % confidence intervals 2.0–11.1). It was also found that the percentage of offspring having both parents with Na ⁺ /Li ⁺ CT activity above the median value was significantly higher in Group A than in Group B (Group A vs Group B: 35 vs 19 %; p < 0.01). On the contrary the percentage of offspring whose erythrocyte Na ⁺ /Li ⁺ CT was lower in both parents was lower in Group A than in Group B: 10 vs 38 %, p < 0.01). Parents of Group A offspring had arterial hypertension more frequently than those of Group B. These results indicate that erythrocyte Na ⁺ /Li ⁺ CT activity is a useful diagnostic tool in identifying normotensive, normoalbuminuric patients who may be predisposed to develop persistent microalbuminuria. This disorder in the cation transport system is associated with poor metabolic control, higher blood pressure, and male sex; it also appears to be, at least partly, genetically transmitted. [Diabetologia (1997) 40: 654–661] Received: 10 September 1996 and in final revised form: 20 February 1997     

Melatonin improves insulin sensitivity independently of weight loss in old obese rats

In aged rats, insulin signaling pathway (ISP) is impaired in tissues that play a pivotal role in glucose homeostasis, such as liver, skeletal muscle, and adipose tissue. Moreover, the aging process is also associated with obesity and reduction in melatonin synthesis from the pineal gland and other organs. The aim of the present work was to evaluate, in male old obese Wistar rats, the effect of melatonin supplementation in the ISP, analyzing the total protein amount and the phosphorylated status (immunoprecipitation and immunoblotting) of the insulin cascade components in the rat hypothalamus, liver, skeletal muscle, and periepididymal adipose tissue. Melatonin was administered in the drinking water for 8‐ and 12 wk during the night period. Food and water intake and fasting blood glucose remained unchanged. The insulin sensitivity presented a 2.1‐fold increase both after 8‐ and 12 wk of melatonin supplementation. Animals supplemented with melatonin for 12 wk also presented a reduction in body mass. The acute insulin‐induced phosphorylation of the analyzed ISP proteins increased 1.3‐ and 2.3‐fold after 8‐ and 12 wk of melatonin supplementation. The total protein content of the insulin receptor (IR) and the IR substrates (IRS‐1, 2) remained unchanged in all investigated tissues, except for the 2‐fold increase in the total amount of IRS‐1 in the periepididymal adipose tissue. Therefore, the known age‐related melatonin synthesis reduction may also be involved in the development of insulin resistance and the adequate supplementation could be an important alternative for the prevention of insulin signaling impairment in aged organisms.     

Persistence of improvement in insulin sensitivity following a dietary weight loss programme

Aim: Short‐term dietary weight loss can improve insulin resistance but long‐term studies are lacking. We sought to quantify the degree to which maintenance of weight loss after a short‐term dietary intervention was associated with persistent metabolic benefits. Methods: Fifty‐seven insulin‐resistant obese subjects had insulin‐mediated glucose disposal quantified through the steady‐state plasma glucose (SSPG) test, and associated metabolic risk markers quantified at baseline, after a 16‐week dietary weight loss intervention, and in 25 subjects, at follow‐up of 28.8 ± 13 months. Changes in metabolic variables over time were analysed and correlation with weight loss ascertained. Those with greatest vs. least long‐term SSPG response (responders vs. non‐responders) were compared. Multivariate analysis was performed for predictors of persistent SSPG response. Results: At follow‐up, the 25 subjects who returned for metabolic testing had, on average, maintained their weight loss. Insulin‐mediated glucose disposal remained significantly improved vs. baseline, as did plasma triglyceride and HDL cholesterol (HDL‐C) concentrations, and improvement correlated with total amount of weight lost. Comparison of SSPG responders to non‐responders showed no difference in amount of weight lost and SSPG change during the 16‐week dietary intervention; however, SSPG non‐responders regained 2.6% of weight lost, whereas responders lost an additional 1.5% at follow‐up (p < 0.05 vs. non‐responders). Non‐responders had baseline characteristics consistent with more severe insulin resistance, including higher fasting plasma glucose (p = 0.03). Long‐term SSPG change was independently predicted by both total weight loss (p = 0.005) and baseline fasting plasma glucose (p = 0.007). Conclusions: Improvement in insulin sensitivity is maintained for 2–3 years following dietary weight loss if weight is not regained. Triglyceride and HDL‐C concentrations also remain improved over time, consistent with improvement in insulin sensitivity. Fasting glucose and weight regain predict less long‐term response in insulin sensitivity. These results highlight the potential long‐term benefits of weight loss and importance of preventing weight regain among high‐risk individuals.     

Elevated sodium-lithium countertransport: a familial marker of hyperlipidaemia and hypertension?

Erythrocyte sodium-lithium countertransport was measured in normolipidaemic and hyperlipidaemic hypertensive patients, hyperlipidaemic normotensive patients and normal controls. Hypertension and hyperlipidaemia were each independently associated with raised sodium-lithium countertransport (by analysis of variance, P less than 0.01 and P less than 0.01). The effects were additive so that hyperlipidaemia could not explain raised sodium-lithium countertransport in hypertension. In hyperlipidaemic hypertensive patients, levels of plasma cholesterol, triglycerides, low-density lipoprotein (LDL) cholesterol and very-low-density lipoprotein (VLDL) cholesterol were increased, and high-density lipoprotein (HDL) cholesterol was reduced. Of these patients, 73.3% had a known family history of hypertension. Their normotensive first degree relatives were studied, and 48% of these also had raised sodium-lithium countertransport and abnormal plasma lipids (raised cholesterol, triglycerides and LDL cholesterol, and reduced HDL cholesterol). Relatives with normal sodium-lithium countertransport had normal lipids. Therefore, raised sodium-lithium countertransport was associated with the inheritance of both hypertension and hyperlipidaemia, and this could explain why raised sodium-lithium countertransport has been associated with a family history of both hypertension and associated cardiovascular disease.     

Apolipoprotein E gene polymorphism is related to metabolic abnormalities, but does not influence erythrocyte membrane lipid composition or sodium-lithium countertransport activity in essential hypertension

The aim of this study was to analyze the influence of the apolipoprotein E (apoE) gene polymorphism on insulin resistance and plasma lipid composition of essential hypertensive patients. A secondary objective was to analyze if differences regarding plasma lipids had an effect on the erythrocyte membrane lipid composition and the activity of the erythrocyte membrane sodium-lithium countertransport. We studied 128 untreated nondiabetic essential hypertensive patients enrolled from our outpatient clinic. We considered as hyperinsulinemic all subjects having more than 80 mU/L of plasma insulin 120 minutes after a 75-g oral glucose intake. The number of hyperinsulinemic subjects among carriers of the epsilon4 allele was higher that in epsilon4 noncarrier subjects (13 of 19 v45 of 109, P < .05; odds ratio [OR], 3.08; confidence interval [CI], 0.99-10.57). Plasma insulin at baseline and plasma insulin and glucose at 120 minutes after overload was higher in carriers of the epsilon4 allele (respectively, 17.5 +/- 6.9 v 12.4 +/- 4.9 mU/L, P < .01; 111.9 +/- 39.9 v 88.7 +/- 48.2, P < .05; and 143.8 +/- 29.3 v 121.2 +/- 30.8 mg/dL, P < .005). Subjects with the epsilon4 allele had a plasma lipid profile more atherogenic than those without this allele. This profile was mainly characterized by higher levels of low-density lipoprotein (LDL) cholesterol (150.1 +/- 31.2 v 133.0 +/- 34.3 mg/dL, P < .05) and very-low-density lipoprotein (VLDL) triglycerides (134.7 +/- 85.5 v 99.2 +/- 68.8 mg/dL, P < .05) and by lower levels of high-density lipoprotein (HDL) cholesterol (41.8 +/- 10.7 v 50.0 +/- 14.7 mg/dL, P < .05). There were no differences between groups regarding erythrocyte membrane cholesterol or phospholipids composition and sodium-lithium countertransport (SLC) activity.     

Red-cell sodium-lithium countertransport and fractional excretion of lithium in normal and hypertensive humans

To examine the relations between erythrocyte sodium-lithium countertransport and renal proximal tubular sodium handling, we measured countertransport, and then subjected 30 normal and 32 hypertensive subjects, both white and black, to provocative maneuvers of volume expansion and contraction. The fractional excretions of sodium and lithium were measured simultaneously. In agreement with previous studies, we found that countertransport in erythrocytes was elevated in hypertensive patients compared with normal subjects. We also observed that whites have a higher level of countertransport than blacks. In the basal state, we found that fractional sodium excretion of hypertensive patients was no different than in normal subjects, whereas the fractional lithium excretion of hypertensive persons was increased compared with normotensive values. Volume expansion with 2 1 0.9% saline administered intravenously during a 4-hour period provoked an exaggerated natriuresis and a greater increase in fractional lithium clearance in hypertensive patients compared with the control group. With volume expansion and contraction, fractional lithium clearance and countertransport were directly correlated. Our data suggest that hypertensive persons do not have increased proximal tubular sodium reabsorption compared with normal subjects. Further, the exaggerated natriuresis of hypertension is, in part, the result of increased distal solute delivery. The fact that our hypertensive patients were older may partially explain the discrepancies between this report and previous observations.     

Relationship between sodium–lithium countertransport and insulin sensitivity in mild hypertension

Objectives. To study the relationship between insulin sensitivity and sodium-lithium countertransport (Na⁺-Li⁺ CT) in mild, essential hypertension, and to investigate the effect of metformin and metoprolol, respectively. Design. A double-blind, triple cross-over, placebo-controlled study over a total period of 18 weeks. Setting. A hypertension out-patient clinic and research laboratory at Sahlgrenska University Hospital. Subjects. Seventeen non-obese men with mild essential hypertension and 17 weight-matched, healthy controls. Interventions. Metformin 850 mg b.i.d., metoprolol CR 100 mg once daily and placebo were given during 18 weeks. Each treatment period was 6 weeks. A euglycaemic clamp was performed and erythrocyte Na⁺-Li⁺ CT measured after each 6-week treatment period. Main outcome measures. Insulin sensitivity, erythrocyte Na⁺-Li⁺ CT, their interrelation, and the effect of metformin and metoprolol CR on both variables, respectively. Results. The hypertensive men tended to have an elevated Na⁺-Li⁺ CT compared with the control subjects (0.34±0.03 versus 0.26±0.02 mmol L^-1  h^-1, P<0.1). Glucose disposal rate was similar, but plasma insulin levels higher (P<0.05) among the hypertensives than the controls. Na⁺-Li⁺ CT exhibited a positive relationship to BMI (r=0.53, P=0.03) and a negative correlation to glucose disposal rate (r=-0.66, P=0.008) in the hypertensive subjects. In multiple regression analysis, Na⁺-Li⁺ CT showed a significant correlation to glucose disposal rate only. In the control subjects, there was no relation between glucose metabolism and Na⁺-Li⁺ CT. Neither metformin nor metoprolol influenced Na⁺-Li⁺ CT, glucose disposal rate or plasma insulin. Conclusion. Erythrocyte Na⁺-Li⁺ CT seemed to be closely related to insulin-glucose metabolism in mild hypertension, but was not influenced by metformin or metoprolol.     

Impaired response to angiotensin II in Type 1 (insulin-dependent) diabetes mellitus. Role of prostaglandins and sodium-lithium countertransport activity

Summary The pathogenesis of diabetic nephropathy remains elusive. A role for renal prostaglandins in antagonizing the hormonal effects of renin-angiotensin II has been postulated as a putative factor leading to hyperfiltration in patients with Type 1 (insulin-dependent) diabetes mellitus. Our aim was to elucidate the effects of angiotensin II on kidney haemodynamics and on blood pressure in eight normal subjects, in nine normotensive, in nine hypertensive with normal sodium-lithium countertransport activity in erythrocytes, in seven hypertensive without and in eight hypertensive Type 1 diabetic patients with microalbuminuria and with high sodium-lithium countertransport activity in erythrocytes. Angiotensin II infusion 4ng·kg^–1·min^–1 for 60 min) decreased the glomerular filtration rate to a greater extent in normal subjects (–20%), than in normotensive patients (–5% p<0.01), in hypertensive patients with normal sodium-lithium countertransport activity in erythrocytes (–8% p<0.01) in hypertensive patients with high sodium-lithium countertransport (–6% p<0.01) and in hypertensive microalbuminuric patients (–5% p<0.01) with Type 1 diabetes. The urinary excretion rate of vasodilatory prostaglandins was two-three fold higher in all patients than in normal subjects. Acute indomethacin treatment restored a normal response to angiotensin II infusion in normotensive patients, but did not change the renal haemodynamic response in normal subjects. With regard to hypertensive patients with and without microalbuminuria indomethacin treatment restored a normal response to angiotensin II in some but not all patients. An inverse relation was found between angiotensin II-induced decrease in the glomerular filtration rate and the sodium-lithium countertransport activity in erythrocytes during indomethacin treatment. Hypertensive and microalbuminuric patients with a sodium-lithium countertransport activity higher than 0.41 mmol·l erythrocyte^–1·h^–1 (the upper limit in normal subjects) also had a greater intimal plus medial thickness of the carotid artery using an ultrasonic imaging technique. Chronic indomethacin administration (30 days) significantly decreased the baseline overnight fasting glomerular filtration rate in normotensive and in hypertensive patients with normal but not in hypertensive and microalbuminuric patients with high sodium-lithium countertransport activity.In conclusion these results demonstrate that: (1) excessive synthesis of vasodilatory prostaglandins antagonizes the regulation of renal haemodynamics by angiotensin II, at least partially accounting for hyperfiltration in Type 1 diabetes, (2) elevated sodium-lithium countertransport activity in erythrocytes identifies a subgroup of patients with Type 1 diabetes and hypertension, with and without microalbuminuria, in whom the normalization of urinary excretion rate of prostaglandins does not restore a normal response to angiotensin II.     

Long-term effects of popular dietary approaches on weight loss and features of insulin resistance

OBJECTIVE: High-carbohydrate (HC)-high-fibre diets are recommended for weight loss and for treating and preventing diseases such as diabetes and cardiovascular disease. We report a randomised trial comparing high-fat (HF) and high-protein (HP) diets with the conventional approach. RESEARCH DESIGN AND METHODS: A total of 93 overweight insulin-resistant women received advice following randomisation to HF, HP or HC dietary regimes, to achieve weight loss followed by weight maintenance over 12 months. Weight, body composition and measures of carbohydrate and lipid metabolism were investigated. RESULTS: Retention rates were 93% for HP and 75% for HC and HF. Features of the metabolic syndrome improved in all groups during the first 6 months, to a greater extent on HF and HP than an HC. During the second 6 months the HF group had increases in waist circumference (mean difference 4.4 cm (95% CI 3.0, 5.8)), fat mass (2.3 kg (1.5, 3.1)), triglycerides (0.28 mmol/l (0.09, 0.46)) and 2 h glucose (0.70 mmol/l (0.22, 1.18)). Overall there was substantial sustained improvement in waist circumference, triglycerides and insulin in the HP group and sustained but more modest changes on HC. Dietary compliance at 12 months was poor in all groups. CONCLUSIONS: HP and HC approaches appear to be appropriate options for insulin-resistant individuals. When recommending HP diets appropriate composition of dietary fat must be ensured. HC diet recommendations must include advice regarding appropriate high-fibre, low glycaemic index foods.