Early influences of nutrition on postnatal growth.

Health and nutrition modulate postnatal growth. The availability of amino acids and energy, and insulin and insulin-like growth factor-I (IGF-I) regulates early growth through the mTOR pathway. Amino acids and glucose also stimulate the secretion of IGF-I and insulin. Postnatal growth induces lasting, programming effects on later body size and adiposity in animals and in human observational studies. Rapid weight gain in infancy and the first 2 years was shown to predict increased obesity risk in childhood and adulthood. Breastfeeding leads to lesser high weight gain in infancy and reduces obesity risk in later life by about 20%, presumably partly due to the lower protein supply with human milk than conventional infant formula. In a large randomized clinical trial, we tested the hypothesis that reduced infant formula protein contents lower insulin-releasing amino acid concentrations and thereby decrease circulating insulin and IGF-I levels, resulting in lesser early weight gain and reduced later obesity risk (the 'Early Protein Hypothesis'). The results demonstrate that lowered protein in infant formula induces similar - but not equal - metabolic and endocrine responses and normalizes weight and BMI relative to breastfed controls at the age of 2 years. The results available should lead to enhanced efforts to actively promote, protect and support breastfeeding. For infants that are not breastfed or not fully breastfed, the use of infant formulas with lower protein contents but high protein quality appears preferable. Cows' milk as a drink provides high protein intake and should be avoided in infancy.

Osteoclastic function is accelerated in male patients with type 2 diabetes mellitus: the preventive role of osteoclastogenesis inhibitory factor/osteoprotegerin (OCIF/OPG) on the decrease of bone mineral density.

To clarify the pathogenesis of altered bone metabolism in diabetic state and its underlying mechanisms, the bone mineral content and fasting levels of serum intact parathyroid hormone (i-PTH), intact osteocalcin (i-OC), tartrate-resistant acid phosphatase (TRAP) and osteoclastgenesis inhibitory factor/osteoprotegerin (OCIF/OPG) were measured in male type 2 diabetic patients and their age-matched controls. In addition, urine levels of osteoclastic markers, C-telopeptide of type I collagen (CTx), deoxypyridinoline (DPD), and N-telopeptide of type I collagen (NTx) were simultaneously determined. Serum levels of i-PTH and i-OC in diabetic patients were significantly lower than those in the controls. Conversely, serum concentrations of TRAP were significantly elevated in diabetic patients. However, no clear correlation was observed between serum i-OC and TRAP. It was also observed that urinary excretion of CTx, DPD, and NTx was significantly increased in the diabetics as compared with the controls. Unexpectedly, serum levels of OCIF/OPG tended to be higher in the diabetic group, and these values exhibited a significantly positive correlation with those of serum TRAP. There was found a significantly negative correlation between serum TRAP and bone mineral density (BMD) and also between serum OCIF/OPG and bone mineral density. It seems probable that OCIF/OPG has a suppressive role on the increased bone resorption to prevent further loss of the skeletal bone mass in type 2 diabetic patients.

Therapeutic effects of psyllium in type 2 diabetic patients.

OBJECTIVE: The aim of this study was to evaluate the effects of psyllium in type 2 diabetic patients. DESIGN: The study included three phases: phase 1 (1 week), phase 2 (treatment, 14 g fibre/day, 6 weeks) and phase 3 (4 weeks). At the end of each phase a clinical evaluation was performed after the ingestion of a test breakfast of 1824.2 kJ (436 kcal). Measurements included concentrations of blood glucose, insulin, fructosamine, GHbA(1c), C-peptide and 24 h urinary glucose excretion. In addition, uric acid, cholesterol and several mineral and vitamin concentrations were also evaluated. SETTING: The study was performed at the Department of Pharmacology, Toxicology and Nursing at the University of León (Spain). SUBJECTS: Twenty type 2 diabetic patients (12 men and 8 women) participated in the study with a mean age of 67.4 y for men and 66 y for women. The mean body mass index of men was 28.2 kg/m(2) and that of women 25.9 kg/m(2). RESULTS: Glucose absorption decreased significantly in the presence of psyllium (12.2%); this reduction is not associated with an important change in insulin levels (5%). GHbA(1c), C-peptide and 24 h urinary glucose excretion decreased (3.8, 14.9 and 22.5%, respectively) during the treatment with fibre (no significant differences) as well as fructosamine (10.9%, significant differences). Psyllium also reduced total and LDL cholesterol (7.7 and 9.2%, respectively, significant differences), and uric acid (10%, significant difference). Minerals and vitamins did not show important changes, except sodium that increased significantly after psyllium administration. CONCLUSIONS: The results obtained indicate a beneficial therapeutic effect of psyllium (Plantaben) in the metabolic control of type 2 diabetics as well as in lowering the risk of coronary heart disease. We also conclude that consumption of this fibre does not adversely affect either mineral or vitamin A and E concentrations. Finally, for a greater effectiveness, psyllium treatment should be individually evaluated.

The short-term effect of dietary pectin on plasma levels and renal excretion of dehydroepiandrosterone sulfate.

Studies specifically investigating the effects of single dietary components on plasma levels of dehydroepiandrosterone (DHEA) and its sulfate ester (DHEAS) are rare. Especially no data is available with regard to specific dietary fibers. Therefore, the impact of pectin (a representative fiber that affects the enterohepatic recirculation of bile acids) was studied in a randomized crossover trial consisting of three diet periods characterized by the same food supply and daily doses of 0 g, 15 g or 30 g pectin. Blood and 24-h-urine samples were collected at the end of each 4-day diet period from 6 healthy male volunteers. Plasma levels of DHEA, cortisol and the major binding protein of DHEAS albumin remained unchanged with the varying pectin supplements. Also, no changes were observed for several urinary analytes including urinary DHEAS. However, effects of pectin intake (30, 15 versus 0 g/d) were seen for plasma DHEAS (9.3 +/- 2.8, 9.2 +/- 2.6, 8.0 +/- 3.1 mumol/L, p < 0.01) and total plasma cholesterol (4.4 +/- 0.7, 4.5 +/- 0.7, 4.7 +/- 0.8 mmol/L, p = 0.1). Obviously, the altered intake of fiber in the form of pectin affects plasma concentrations of DHEAS and cholesterol in an opposite direction. The reason for this is not known but a dietetically induced modulation of the binding properties of plasma albumin for DHEAS appears possible. Our findings suggest that the target tissue-available, not protein-bound fraction of circulating DHEAS (as reflected by the renal DHEAS output) is not necessarily altered when total plasma concentrations of DHEAS vary.

Protein intake in early infancy: effects on plasma amino acid concentrations, insulin metabolism, and growth.

The effects of different protein intakes on wt gain, insulin secretion, and plasma concentrations of amino acids have been evaluated in a prospective study involving 30 normal term infants. The infants were studied from 4.0 to 6.0 mo of age. Ten infants were breast-fed (BF), the others were randomly divided into two groups of 10 infants. One group was fed a formula containing 1.3 g protein/100 mL (F 1.3), the other a formula with 1.8 g protein/100 mL (F 1.8). The formulas were isocaloric (72 kcal/100 mL), and the fat concentrations were 3.5 g/100 mL (F 1.3) and 3.2 g/100 mL (F 1.8). All infants received the same supplementary foods. The urinary C-peptide excretion in the infants fed the F 1.8-formula was 4.4 +/- 2.1 nmol/mmol creatinine or 19.4 +/- 12.9 nmol/m2, significantly higher than that in the infants fed the F 1.3-formula (2.6 +/- 1.5 and 7.9 +/- 5.1) or the BF infants (1.7 +/- 1.4 and 6.3 +/- 6.0). Gain in wt was 18.0 +/- 4.3, 19.9 +/- 3.9, 22.8 +/- 1.6 g/kg/wk and corresponded to protein intakes of 1.3 +/- 0.2, 1.9 +/- 0.3, and 2.6 +/- 0.2 g/kg/d, in the BF, F 1.3, and F 1.8 groups, respectively. Gain in length was 6.7 +/- 1.8 (BF-group), 6.2 +/- 2.5 (F 1.3-group), and 7.6 +/- 2.2 (F 1.8-group) mm/m/wk. Wt gain correlated with urinary C-peptide excretion at 6.0 mo (r = 0.51, p less than 0.01) and with protein intake (r = 0.43, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Fasting plus prandial insulin supplements improve insulin secretory ability in NIDDM subjects.

To examine how insulin secretory ability is modified by strict glycemic control in non-insulin-dependent diabetes mellitus (NIDDM) subjects, basal and/or prandial insulin was supplemented for 4 wk in 24 diabetic subjects who were secondary failures to sulfonylurea treatment. One intermediate-acting insulin injection a day (n = 7) failed to suppress the rise in plasma C-peptide after meals and did not improve plasma C-peptide responses during a posttreatment oral glucose challenge. Continuous subcutaneous insulin infusion with a premeal bolus (n = 8) suppressed both fasting and meal-related rises in C-peptide and improved C-peptide response during the posttreatment oral glucose challenge. Daily insulin requirements during the 4 wk of treatment were reduced significantly by 52%. A short-acting insulin injection before each meal (n = 9) without basal supplementation suppressed the prandial rise in C-peptide and was associated with a significant reduction in daily insulin requirements during 4 wk of treatment by 28%. Diabetic subjects whose fasting and prandial hyperglycemia were less than 140 and less than 200 mg/dl, respectively, showed a significantly higher C-peptide response during oral glucose challenge after treatment than those whose insulin treatment only normalized (less than 200 mg/dl) prandial but not basal hyperglycemia (greater than 140 mg/dl). These results suggest that a short-term period of meal-related insulin treatment (which normalized prandial glycemia) increases residual beta-cell function in NIDDM subjects who failed long-term sulfonylurea administration. A basal insulin supplement alone was not effective. The effectiveness of a prandial insulin supplement may have been further improved by a combined basal and meal-related treatment program.

The safety and efficacy of a controlled low-energy ('very-low-calorie') diet in the treatment of non-insulin-dependent diabetes and obesity.

We evaluated the safety and efficacy of a highly supplemented controlled low-energy (1764 kJ [420 kcal]) diet in the treatment of non-insulin-dependent diabetes and obesity. Six obese, diabetic women ranging from 143% to 297% of ideal body weight were studied in a metabolic ward for 48 days. The subjects ingested a weight-maintenance diet during an eight-day control period followed by 40 days of an experimental diet containing 1764 kJ (420 kcal) of a mixture of protein (43% of energy intake), carbohydrates (51%), and fat (6%), supplemented with minerals, trace elements, and vitamins. The subjects were monitored for balances of nitrogen and minerals, as well as for the appearance of cardiac arrhythmias by 24-hour electrocardiographic recordings. Weight loss was rapid and sustained and averaged 10.1% +/- 0.8% over 40 days. Fasting plasma glucose levels declined from 16.2 +/- 1.9 mmol/L (293 +/- 36 mg/dL) to 6.9 +/- 0.8 mmol/L (126 +/- 16 mg/dL) by day 35. Similarly, hemoglobin A1c levels fell from 0.11 +/- 0.009 (11.2% +/- 0.9%) to 0.8 +/- 0.001 (8.2% +/- 1.1%). Urinary C-peptide levels declined from 62.2 +/- 15.6 nmol/48 h to 20.0 +/- 5.9 nmol/48 h by days 39 to 40 and paralleled the decline in plasma glucose values, the majority of which occurred in the first seven days. Concentrations of serum cholesterol and triglycerides decreased. Balances for nitrogen, potassium, and magnesium were negative at -1.7 g/24 h, -2.2 mEq/24 h, and -2.9 mg/dL, respectively. Blood pressure decreased without orthostasis. Resting metabolic rate fell a mean of 18% but remained within normal limits. Triiodothyronine levels also declined. Twenty-four-hour ambulatory electrocardiographic readings disclosed no significant bradyarrhythmia or tachyarrhythmia for any patient. These studies, based on a limited number of subjects, demonstrate that a highly supplemented controlled low-energy diet is a safe and efficacious treatment for diabetes and obesity, leading to significant decreases in weight, blood pressure, and levels of plasma glucose and plasma lipids. Such diets may be the optimal initial treatment of moderate to markedly obese patients with non-insulin-dependent diabetes.

Assessment of the metabolic effects of dietary carbohydrate and fibre by measuring urinary excretion of C-peptide.

An assessment of the metabolic effect of dietary carbohydrate on daily insulin secretion, reflected by the 24-h urine output of C-peptide, has been made. Urinary C-peptide excretion increased when the carbohydrate intake of 6 normal subjects was increased from 200 to 400 g. A high-fibre diet rich in beans and lentils caused a significant fall in urine C-peptide and a lowering of blood glucose values in both normal and diabetic subjects. This confirms the insulin-sparing effect of leguminous foods. An increase of dietary fibre to 50 g mainly as cereal fibre did not significantly alter urine C-peptide excretion in normal subjects. Urinary C-peptide estimations could be useful for assessing the effect of different diets on daily insulin secretion.