Reticulocyte hemoglobin equivalent to detect thalassemia and thalassemic hemoglobin variants.

INTRODUCTION: Thalassemia and iron deficiency may both result in hypochromic microcytic anemia. Hematological algorithms that differentiate the two are mainly established in adult selected diagnostic groups. We aimed at creating an algorithm applicable in the presence of children, hemoglobin variants, and iron deficiency. METHODS: Our study material constituted blood samples referred during 1 year for routine diagnostics of hemoglobinopathy. We included 443 samples, of which 37% were from children 3 months or older. We found ß-thalassemia trait (n = 100), α-thalassemia (n = 75), combined α-/ß-thalassemia (n = 14), hemoglobin variants (n = 42), and no-hemoglobinopathy (n = 207), of whom 107 had a ferritin at or below 20 µg/L. We included reticulocyte hemoglobin equivalent, ferritin, and erythrocyte count in our algorithm. RESULTS: Our algorithm differentiated ß-thalassemia trait from no-hemoglobinopathy with a sensitivity of 99% at 83% specificity. It performed better than other published algorithms when applied to all patient samples, while equally or moderately better in the 63% adult samples. Our algorithm also detected the clinically significant α-thalassemias, and most of the combined α-/ß-thalassemias and thalassemic hemoglobin variants. CONCLUSION: Our algorithm efficiently differentiated thalassemia and thalassemic hemoglobin variants from iron deficiency in children and adults.

Combined diet and exercise intervention reverses the metabolic syndrome in middle-aged males: results from the Oslo Diet and Exercise Study.

We examined the single and combined effects of a 1-year diet and exercise intervention on the International Diabetes Federation (IDF) metabolic syndrome among middle-aged males. The study was a randomized, controlled, 2 x 2 factorial intervention study. Participants included 137 men with metabolic syndrome according to the IDF criteria aged 40-49 years randomly allocated to four intervention groups: diet alone (n=34), exercise alone (n=34), the combination of the diet and exercise intervention (n=43) or control (n=26). The main outcome measure was metabolic syndrome as defined by IDF criteria (2005). In the combined diet and exercise group, 14 participants (32.6%) (P<0.0001 as compared with control) had the metabolic syndrome after 1-year intervention. In the diet-only group, 22 participants (64.7%) (P=0.023 vs control) and in the exercise-only group 26 participants (76.5%) (P=0.23 vs control) had the metabolic syndrome following the intervention. Utilizing the factorial design, both dietary and exercise intervention had significant effects (P<0.005) on the resolution of the metabolic syndrome. Both exercise and dietary intervention reduced metabolic syndrome prevalence compared with control after 1 year of intervention. However, the combined diet and exercise intervention was significantly more effective than diet or exercise alone in the treatment of the metabolic syndrome.

Effect of Traditional Beer Consumption on the Iron Status of A Rural South African Population

Objective.To determine the effect of traditional beer consumption on the iron status of rural black subjects.Design. A cross-sectional study was undertaken.Setting. Dikgale field site and the surrounding villages in Limpopo Province; South Africa.Subjects. Eight hundred and forty-four non-alcohol consumers (738 women and 106 men) and 280 alcohol consumers (163 women and 117 men) aged 30 years and above; participated in the study.Outcome measures. Outcome measures included alcohol consumption; serum ferritin levels; percentagetransferrin saturation; total iron-binding capacity; haemoglobin and C-reactive protein levels.Results. Traditional beer fermented in either iron pots or plastic containers was found to have iron levels ranging from 15 mg/l to 67.8 mg/l and 6 mg/l to 17 mg/l; respectively. Iron status as measured by serum ferritin; serum iron; percentage transferrin saturation; and haemoglobin levels was significantly higher in alcohol consumers than in non-consumers; even after adjustment for age and C-reactive protein (CRP) levels. A high percentage of women (12.3) and men (8.2) consuming alcohol had iron overload.Conclusion. This study showed that consumption of traditional beer in a non-urban population in Limpopo Province was associated with high levels of markers of iron status. Traditional beer consumption seemed to prevent iron deficiency in those at risk of developing such deficiency; but appeared to precipitate iron overload in those at risk of developing iron overload

Reference intervals for eight enzymes in blood of adult females and males measured in accordance with the International Federation of Clinical Chemistry reference system at 37 degrees C: part of the Nordic Reference Interval Project.

As part of the Nordic Reference Interval Project we present reference intervals for alanine transaminase (ALT), aspartate transaminase (AST), creatine kinase (CK), lactate dehydrogenase (LD), alkaline phosphatase (ALP), gamma-glutamyltransferase (GT), amylase (AMY) and pancreatic type of AMY in blood of adult males and females. A total of 3036 reference persons, all of whom considered themselves to be in good health, were recruited by 102 Nordic clinical biochemical laboratories. Exclusions were undertaken on the basis of predefined biochemical and clinical criteria. Enzyme activities in serum and plasma were measured in the different laboratories using various commercially available routine measurement systems at 37 degrees C. Only results obtained with the International Federation of Clinical Chemistry (IFCC) compatible measuring systems were selected for estimation of the enzyme reference intervals. The final number of results on each enzyme varied from 459 (LD) to 2300 (ALT). The 2.5 and 97.5 percentile reference limits were calculated by a non-parametric method in accordance with the IFCC recommendations, using the Refval 4.0 data program. Statistical partitioning testing was undertaken to decide whether the reference intervals ought to be partitioned according to gender and/or age. For most of the enzymes, but not for all, the upper reference limits were found to be higher than those that have been in general use until now.

Does short-term smoking cessation reduce plasma total homocysteine concentrations?

Both elevated plasma total homocysteine and cigarette smoking are associated with an increased risk of occlusive cardiovascular disease. We examined whether smoking cessation for a mean time of 10-11 weeks lowered plasma total homocysteine concentrations in men and women with (n=59) and without (n=55) established cardiovascular disease. Blood tests were available for 58 quitters and 29 subjects who did not stop smoking. Compared with subjects who continued to smoke, quitters had statistically significant higher HDL cholesterol concentrations, but plasma total homocysteine concentrations did not differ between the two groups. Likewise, no differences were found between quitters and non-quitters whose baseline homocysteine concentrations were above the 75th percentile.

Effect of long-term changes in diet and exercise on plasma leptin concentrations.

BACKGROUND: Although it is known that plasma leptin concentrations correlate with the amount of adipose tissue in the body, little information is available on the long-term effects on leptin concentrations of changes in diet and exercise. OBJECTIVE: We wanted to examine whether changes in dietary energy sources and exercise-mediated energy expenditure, alone or in combination, affect plasma leptin concentrations. DESIGN: In a randomized, 2 x 2 factorial trial, 186 men with metabolic syndrome were divided into 4 groups: diet, exercise, a combination of diet and exercise, and control. Data on dietary intake, physical fitness, and demographics were collected and plasma leptin concentrations were measured before and after a 1-y intervention period. RESULTS: Plasma leptin concentrations, body mass index, and fat mass decreased in association with long-term reductions in food intake as well as increased physical activity. By adjusting for either body mass index or fat mass, we observed a highly significant reduction in plasma leptin concentration after both the diet and the exercise interventions. There was no interaction between the interventions, suggesting a direct and additive effect of changes in diet and physical activity on plasma leptin concentrations. CONCLUSION: Long-term changes in lifestyle consisting of decreased intake of dietary fat and increased physical activity reduced plasma leptin concentrations in humans beyond the reduction expected as a result of changes in fat mass.

Structure and composition of common bile duct stones in relation to duodenal diverticula, gastric resection, cholecystectomy and infection.

BACKGROUND: Common bile duct stones represent a clinical problem often involving severe infection, cholangitis and cholestasis. Stasis and infection are thought to play a part in the pathogenesis of choledocholithiasis. Investigations on the etiology of common bile duct stones are, however, scarce because of the difficult access to common bile duct stones and bile. In a clinical series of common bile duct stones, we studied the gross appearance of stones extracted endoscopically from the common bile duct and measured the cholesterol and bilirubinate content in order to elucidate factors of importance to etiology. METHODS: In 135 patients treated endoscopically for bile duct stones, the stones or parts of the stones were collected. Appearances of the cut surface of the stones were studied and described. Cholesterol and bilirubinate content were analyzed enzymatically and with infrared spectroscopy. The growth in bile of gas-producing bacteria previously shown to be correlated with enterobacteriacea was investigated. RESULTS: Seventy-five percent of the stones were pigment stones, the majority with concentric pigmented layering. There was good agreement between cholesterol measurements. With a cutoff at 50% for the infrared measurements and 25% for the enzymatic assay only 3 stones were discordant between cholesterol measurements and visual inspection. Twenty-one of 23 patients with a previous Billroth-II gastric resection had pigment stones (p < 0.05). Gas-producing bacteria were significantly more prevalent in the bile from patients with layered pigment stones. CONCLUSION: Pigment stones with concentric layering highly suggestive of a cyclic process of crystallization were recovered from the common bile duct in 70% of the patients in our series.

Brown pigment stones in the common bile duct: reduced bilirubinate diconjugate in bile.

BACKGROUND: Bilirubin is the main component of most common bile duct stones. Normally, almost all bilirubin in bile is conjugated to glucuronic acid or some other sugar moiety. These conjugates are unstable and liable to deconjugation. Unconjugated bilirubin is insoluble and may precipitate as the calcium salt found in brown pigment stones. The pattern of bilirubin conjugates in common duct bile of patients with choledocholithiasis has been unknown. METHODS: In a clinical series of 55 patients with choledocholithiasis common-duct bile was aspirated, and the bilirubin conjugates analyzed with high-performance liquid chromatography. One stone from each patient was analyzed for cholesterol and bilirubin content to determine stone type. RESULTS: Sixteen patients had cholesterol stones, 38 patients had brown pigment stones, and 1 patient had a black stone. Patients with pigment stones had a lower percentage of bilirubin diglucuronide (median, 60.3%; interquartile range, 49.7%-67.3%) than patients with cholesterol stones (64.0%; 60.2%-73.3%) (Mann-Whitney, P=0.015). No significant difference was found for the other bilirubin conjugates, total bilirubin, or biliary pH when pigment and cholesterol stone patients were compared. The time of bile sampling in relation to papillotomy and treatment of cholestasis was not associated with the low percentage of bilirubin diglucuronide. The observation of reduced values for bilirubin diglucuronide could not be ascribed to duodenal diverticula or Billroth-II gastric resection. CONCLUSION: The percentage of the main bilirubinate conjugate, bilirubin diglucuronide, is decreased in the common duct bile of patients with pigmented compared with cholesterol stones.

Urinary iodine concentrations and thyroid function in adult Zimbabweans during a period of transition in iodine status.

BACKGROUND: In 1993 the compulsory iodization of salt was introduced in Zimbabwe, a country that was previously an area of severe iodine deficiency. OBJECTIVE: The objective of this study was to document urinary iodine excretion and biochemical thyroid function in seemingly healthy, community-dwelling adults after the introduction of iodization. DESIGN: A multistage, random sampling method was used in rural and urban settings to identify households from which the senior household member (aged >35 y) was recruited (alternating male and female recruits). Demographic data were collected for each subject and urinary and venous blood samples were taken. Urinary iodine excretion and serum thyroid hormone status (thyrotropin and total thyroxin) were evaluated according to age, sex, and area of residence. RESULTS: A total of 736 adults were recruited (253 men; mean age: 64 y). Urinary iodine concentrations were high [median (first and third quartiles): 4.41 (2.84, 6.78) micromol/L, or 560 (360, 860) microgram/L] and were significantly higher in rural areas than in urban areas [4.73 (3.07, 7.14) micromol/L, or 600 (390, 906) microgram/L, compared with 3.47 (2.05, 4.73) micromol/L, or 440 (260, 600) microgram/L; P < 0.001]. Urinary iodine excretion declined significantly with increasing age (r = -0.29, P < 0.001). Serum thyroid status suggested that the prevalence of biochemical hyperthyroidism in the study was 3%, with 13 of 415 cases in rural and 3 of 149 cases in urban subjects. CONCLUSION: This study reaffirms the need to continuously monitor iodine replacement programs to ensure efficacy.

Beta-thromboglobulin in urine and plasma: influence of coronary risk factors.

Blood platelet activation in vivo was evaluated by measuring beta-thromboglobulin in plasma and high molecular weight beta-thromboglobulin in urine in hypertensive smoking and nonsmoking middle-aged men (n=36) and in normotensive age-matched controls (n=40). We found no significant linear relationships between nocturnal or resting urinary high molecular weight beta-thromboglobulin and plasma beta-thromboglobulin in the combined hypertensive and normotensive groups. The excretion of high molecular weight beta-thromboglobulin correlated significantly with diastolic blood pressure when all subjects were pooled. After 60 minutes supine rest, nonsmokers had higher excretion of high molecular weight beta-thromboglobulin than smokers. Plasma beta-thromboglobulin levels tended to be higher in hypertensives. In multivariate analyses, resting high molecular weight beta-thromboglobulin excretion was positively related to diastolic blood pressure and negatively related to smoking, whereas plasma beta-thromboglobulin was positively related to diastolic blood pressure and inversely related to apolipoprotein A1 and B. We conclude that urinary high molecular weight beta-thromboglobulin and plasma beta-thromboglobulin are not closely related, but are complementary analyses, as there are methodological confounders for both variables.

Associations between central obesity and indexes of hemostatic, carbohydrate and lipid metabolism. Results of a 1-year intervention from the Oslo Diet and Exercise Study.

The relationships of central obesity and physical fitness to indexes of hemostatic, lipid and glucose metabolism both at baseline and after 1 year of diet and exercise intervention were examined in 209 sedentary middle-aged men and women with increased coronary risk factor levels. Central obesity was measured as either waist circumference or waist/hip ratio. Maximal oxygen uptake was used as a measure of physical fitness. The cross-sectional results show that there were significant correlations between waist circumference and euglobuline clot lysis time (r = 0.23), factor VII (r = 0.16), glucose and insulin before and after 1 h glucose load (r ranging from 0.32 to 0.50). The 1-year intervention gave the following associations between changes in waist circumference and changes in: euglobuline clot lysis time (r = 0.27), factor VII (r = 0.19), carbohydrate variables and lipids (magnitude of r ranging from 0.19 to 0.43). Also the other indexes of obesity and physical fitness showed significant correlations to indexes of hemostatic, lipid and glucose variables, both cross-sectionally and for changes after the 1-year intervention. The associations between changes in central obesity and changes in indexes of hemostatic, carbohydrate and lipids were generally stronger during 1 year of diet and exercise intervention than those found at baseline. Multiple regression analyses with waist circumference, waist/hip ratio, percent body fat and Vo2 max as independent variables and indexes of hemostatic, carbohydrate and lipid metabolism as dependent variables showed that waist circumference was a significant predictor for indexes of the hemostatic, carbohydrate and lipid metabolism, mostly independent of physical fitness. The cross-sectional and 1-year change results support each other and therefore underscore the importance of abdominal obesity as an important risk factor for cardiovascular disease.

Use of fish oils appears to reduce infarct size as estimated from peak creatine kinase and lactate dehydrogenase activities.

In 753 patients with acute myocardial infarction, use of fish oils (FO, n = 242) before onset of infarction seemed to reduce infarct size as estimated from peak creatine kinase (CKmax) and lactate dehydrogenase (LDmax) activities. The study had an observational exposed/nonexposed design, and both crude and adjusted effects were looked for. CRUDE EFFECTS: In the restricted cohort of patients not receiving thrombolytic treatment (n = 411), FO reduced CKmax from 879 to 759 U/l (2 p = 0.030) and LDmax from 870 to 768 U/l (2 p = 0.011), respectively. More of these patients in the lowest enzyme quartiles used FO, p for linear trend was for CKmax 0.008 and for LDmax 0.06, respectively. ADJUSTED EFFECTS: In patients not receiving thrombolytic treatment, FO reduced CKmax (2 p = 0.007) and LDmax (2 p = 0.005), but in patients receiving such treatment, CKmax and LDmax values increased, 2 p being 0.036 and 0.097, respectively. In patients not receiving thrombolysis, FO increased the incidence of small infarcts (the 25% quartile), odds ratio for CKmax was 1.82 (2 p = 0.018) and for LDmax 1.66 (2 p = 0.048), respectively. The results indicate that FO may reduce infarct size and the incidence of large infarcts. In addition, FO seems to enhance the effect of thrombolysis.

Serum lipids in postmenopausal or perimenopausal women using estrogen alone, estrogen with levonorgestrel, or estrogen with norethisterone, compared with nonusers: results from a cross-sectional study in two Norwegian counties 1985-1988.

The aim of this study was to compare, in a population setting of postmenopausal or perimenopausal women aged 40 to 54, the levels of serum lipids in women using different hormone replacement therapy (HRT) regimens with women using no sex hormones. There was no unequivocal tendency of a more healthy lifestyle among those using HRT than among nonusers. Any type of regimen was associated with a lower mean level of total and calculated low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol was 0.08 mmol/L (5.2%) higher in those using estrogen alone, 0.07 mmol/L (4.5%) higher in users of HRT with norethisterone, and 0.07 mmol/L (4.5%) lower in users of HRT with levonorgestrel, compared with nonusers. The ratio of total-to-HDL cholesterol was lower by 0.37 (6.1%) in those using estrogen alone, by 0.65 (12.3%) in those using HRT with norethisterone, and by 0.24 (5.3%) in those using estrogen with levonorgestrel. There was no association between body mass index and HDL-cholesterol among women who used HRT with norethisterone, whereas an inverse relationship was present in those using estrogen alone and in nonusers (P [interaction] < 0.05).

Monday and non-Monday concentrations of lifestyle-related blood components in the Oslo Diet and Exercise Study.

OBJECTIVE: We hypothesized that participants of intervention studies have an unfavourable lifestyle at the weekend compared with the rest of the week, thus affecting the concentrations of components in samples drawn on Mondays. DESIGN: The hypothesis was examined using data from the Oslo Diet and Exercise Study, a 2 x 2 randomized intervention trial on diet and exercise involving 209 participants. Each person chose which day of the week to attend for blood sampling, both before and after the 1 year of intervention. MAIN OUTCOME MEASURES: Comparison of mean concentrations of the components measured, in samples drawn on Mondays vs. non-Mondays, both at the start and at the end of intervention. RESULTS: At the start, nine components, from haemostasis, carbohydrate and lipid metabolism, showed a difference of more than 10% between Monday and non-Monday values, all Monday values differing from the non-Monday values in a cardiovascularly unfavourable direction. Participants starting and ending on a Monday showed the unfavourable profile both times, and those who were examined both times on a non-Monday showed a consistently favourable profile, whereas those who changed the day of examination at the start and end changed profile accordingly. CONCLUSION: The lifestyle-related components examined here showed differences between Monday and non-Monday values, which were not due to a selection bias. We suggest they may be related to a different lifestyle at the weekend compared with ordinary working days. If such effects are not recognized and properly taken into account, they may markedly affect the outcome of intervention studies.

Flow cytometric measurement of low density lipoprotein receptor activity validated by DNA analysis in diagnosing heterozygous familial hypercholesterolemia.

We have evaluated whether low density lipoprotein (LDL) receptor activity of stimulated lymphocytes, as measured by an improved flow cytometric assay, may be used to diagnose familial hypercholesterolemia (FH). Cells were isolated from 75 children suspected from strict clinical criteria to be FH heterozygotes and from 29 normal children. DNA from the FH patients were also subjected to molecular genetic analysis of the LDL receptor gene in order to confirm the clinical diagnosis. A molecular genetic diagnosis of FH was obtained in 68 of the 75 patients; 67 of these had a low (below 70% of normal) receptor activity and 1 had a borderline (71%) activity. By contrast, 28 of the normal children showed a normal (above 80%) and 1 a borderline (78%) receptor activity. Of the 7 patients in whom no mutation in the LDL receptor gene was found, 4 showed a normal, 1 a borderline, and 2 showed a low activity. In summary, measurement of LDL receptor activity allowed us to separate between genetically diagnosed FH heterozygotes and healthy children. The combined use of LDL receptor activity measurements and molecular genetic analysis allows us both to diagnose and exclude FH in children suspected to suffer from this disease.

Serum N-terminal pro-atrial natriuretic factor 1-98 before and during thyroxine replacement therapy in severe hypothyroidism.

Decreased plasma concentrations of atrial natriuretic factor (ANF) and of its N-terminal prohormones have been demonstrated in severely hypothyroid patients compared with control subjects, and shown to normalize with thyroxine (T4) replacement therapy. Whether this depends on thyroid hormone deficiency exclusively or is secondary to hemodynamic changes that result from it remains a matter of debate. In a recent investigation dose-related increases in both ANF and N-terminal prohormones of ANF by T4 replacement therapy in incremental doses increased at 4-week intervals were demonstrated. It was suggested that thyroid hormones may enhance synthesis rather than release of atrial peptide hormones. The aim of the present study was to confirm this assumption in hypothyroid patients with normal cardiac performance. Serum N-terminal amino acids 1-98 (ie, pro-ANF 1-98) of pro-ANF was determined in 11 severely hypothyroid patients without pericardial effusion and with normal cardiac left ventricular function. Mean pro-ANF 1-98 concentration before T4 replacement therapy remained unchanged after 10 days on T4 (p = .12). After 2 months of therapy, mean pro-ANF 1-98 was significantly increased compared with pretreatment values (p < .003). A significant correlation to the increase in free T4 (r = 0.48, p < .01) but not to the decrease in thyrotropin (TSH) (r = -0.32, p = .09) was found. The present results indicate that thyroid hormones directly increase pro-ANF 1-98 independently of cardiac hemodynamics in the hypothyroid state.

Blood lipid and lipoprotein levels and the risk of cancer of the colon and rectum. A prospective study of 62,173 Norwegian men and women.

BACKGROUND: Concern has been raised that a low total serum cholesterol level, although beneficial for cardiovascular diseases, may increase the risk of cancer. This prospective cohort study analyses the hypotheses that a low total serum cholesterol level or its subfractions (serum low-density-lipoprotein cholesterol, high-density-lipoprotein cholesterol, and triglycerides) increase the risk of cancer of the colon and rectum. METHODS: Between 1977 and 1983, 62,173 men and women attended a health screening carried out by the Norwegian National Health Screening Service. The screening consisted of a questionnaire, anthropometric measurements, and samples of non-fasting blood drawn for analyses of serum total cholesterol, low-density-lipoprotein cholesterol, high-density-lipoprotein cholesterol, and triglycerides. RESULTS: During the 7- to 13-year follow-up, 186 patients were found to have colon cancer and 106 rectal cancer by linkage to the Norwegian Cancer Registry. Among men there were no associations between blood lipid and lipoprotein levels and risk of cancer of the proximal colon, distal colon, or the rectum. Among women there was a formal statistically significant inverse relationship between level of total cholesterol and low-density-lipoprotein cholesterol and risk of distal colon cancer, and a positive trend between total cholesterol level and rectal cancer. CONCLUSIONS: The statistically significant results among women were interpreted as incidental, and we conclude that blood lipid and lipoprotein levels were not associated with the risk of colon or rectum cancer in men or women in this cohort.

Lifestyle changes may reverse development of the insulin resistance syndrome. The Oslo Diet and Exercise Study: a randomized trial.

OBJECTIVE: To compare and assess the single and joint effect of diet and exercise intervention for 1 year on insulin resistance and the development leading toward the insulin resistance syndrome. RESEARCH DESIGN AND METHODS: An unmasked, randomized 2 x 2 factorial intervention trial was applied with a duration of 1 year for each participant. The trial comprised 219 men and women with diastolic blood pressure of 86-99 mmHg, HDL cholesterol < 1.20 mmol/l, triglycerides > 1.4 mmol/l, total cholesterol of 5.20-7.74 mmol/l, and BMI > 24 kg/m2. Participants were randomly allocated to diet group (n = 35), diet and exercise group (n = 67), exercise group (n = 54), and control group (n = 43). The diet included increased intake of fish and reduced total fat intake. The exercise program entailed supervised endurance exercise three times a week. Baseline cross-sectional changes and 1-year changes in insulin resistance, fasting serum levels of insulin, C-peptide, proinsulin, glucose, and lipids as well as weight, mean blood pressure, and plasminogen activator inhibitor 1 (PAI-1) values were recorded. RESULTS: The cross-sectional results at baseline showed significant correlations between the calculated insulin resistance and BMI (r = 0.54) and correlations between the mean blood pressure (mBP) (r = 0.26) and PAI-1 (r = 0.40). The 1-year diet intervention gave a significant decrease in the calculated insulin resistance from 4.6 to 4.2 and a positive correlation between the changes in insulin resistance and changes in BMI (r = 0.40). The diet and exercise intervention also led to significantly decreased insulin resistance (from 5.0 to 4.0). The exercise intervention did not significantly change insulin resistance. CONCLUSIONS: The cross-sectional and 1-year intervention results supported each other and underscored the important connection between increased BMI and the development leading toward the insulin resistance syndrome.