Trans fatty acids, insulin resistance, and type 2 diabetes

Type 2 diabetes, a growing global health problem, has a complex etiology involving many interactions between genetic and environmental factors. Essential to the development of the disease is insulin resistance of the peripheral tissues. Insulin resistance may be partly modified by the specific types of dietary fatty acids. Trans fatty acids (TFAs), created through the transformation of polyunsaturated fatty acids from their natural cis form to the trans form, are abundant in the Western diet. TFAs take on similar properties as saturated fats, and appear to be more atherogenic. High intakes of saturated fats may promote insulin resistance. It is therefore reasonable to hypothesize that high intakes of TFAs would have similar, or stronger, effects. In this review, all current evidence on the topic of TFAs, insulin resistance, and type 2 diabetes is summarized and interpreted. Although there is some support from observational and experimental studies for the hypothesis that high intakes of TFAs may increase the risk for type 2 diabetes, inconsistencies across studies and methodological problems make it premature to draw definitive conclusions at this time. More experimental research in humans is needed to further address this question.     

妊娠期糖尿病孕妇血清ω-3脂肪酸与胰岛素抵抗关系的研究

摘要:目的　探究妊娠期糖尿病孕妇空腹血清ω-3脂肪酸水平对胰岛素抵抗的影响。方法　测定40例妊娠期糖尿病孕妇（GDM组）、40例正常妊娠孕妇（正常妊娠组）空腹血清ω-3脂肪酸、胰岛素、血糖、糖化血红蛋白（HbA1c）水平;并计算2组孕妇胰岛素抵抗指数（Insulin Resistance IRI）。结果　GDM组孕妇空腹血清ω-3脂肪酸水平较正常妊娠组明显减少,2组比较差异有统计学意义（t＝26.78,P＜0.05）;GDM组孕妇IRI、空腹血糖、胰岛素、HbA1c水平明显高于正常妊娠组,2组比较差异有统计学意义（t＝32.56,t＝18.25,t＝15.31,t＝13.24,P＜0.05）。（2）GDM组孕妇血清ω-3脂肪酸水平与IRI、空腹血糖、HbA1c呈负相关（r＝-0.812,r＝-0.545,r＝-0.296,P＜0.05）,与胰岛素水平无相关性（r＝0.197,P＞0.05）。正常妊娠组孕妇血清ω-3脂肪酸与IRI呈负相关,（r＝-0.280,P＜0.05）,相关性小于GDM组,正常妊娠组孕妇ω-3脂肪酸水平与胰岛素、血糖、HbA1c无相关性（r＝0.213、0.179、0.195）。结论　提高GDM孕妇血清ω-3脂肪酸含量可减轻其胰岛素抵抗的程度。     

Role of fatty acids in the development of insulin resistance and type 2 diabetes mellitus

Insulin resistance is defined as the reduced responsiveness to normal circulating levels of insulin. It is the basic condition of type 2 diabetes mellitus, in which both experimental animals and humans accumulate lipids intracellularly in skeletal muscle and liver. Measurement of these lipids in humans, using nuclear magnetic resonance spectroscopy after lipid infusion, indicated they could cause inhibition of the glucose transporter GLUT4, thereby suppressing glucose entry into cells and inhibiting glucose oxidation and glycogen synthesis in muscle. Furthermore, it is known that the enzyme acetyl-CoA carboxylase2 (ACC2) suppresses the oxidation of fatty acids by inhibiting the entry of fatty acids into mitochondria. Further support for the lipocentric hypothesis of the pathogenesis of insulin resistance was provided by knocking out the gene coding for ACC2 in mice; this led to greater fatty acid oxidation, reduced fat mass and, in consequence, greatly enhanced insulin sensitivity. These studies suggest that a specific inhibitor of ACC2 would have therapeutic potential for type 2 diabetes mellitus.     

细胞因子与2型糖尿病及胰岛素抵抗的相关性研究

目的 研究2型糖尿病及胰岛素抵抗患者白细胞介素6（IL-6）、白细胞介素8（IL-8）及肿瘤坏死因子α（TNF—α）的变化，分析细胞因子与糖尿病及胰岛素抵抗的相关性。方法 采用酶联免疫吸附法测定90例2型糖尿病患者及30例正常人血清各细胞因子浓度，并同时测定空腹血糖（FPG）、糖化血红蛋白、空腹胰岛素（FINS）及空腹C肽（FCP）水平，分析其与细胞因子的相关性。结果 与正常对照组比较2型糖尿病组血清细胞因子的含量均明显增高（P〈0．01、P〈0．05）；胰岛素抵抗组的IL-6、TNF—α升高与非胰岛素抵抗组比较差异有统计学意义（P〈0．05），胰岛素抵抗与细胞因子的增高密切相关。结论 2型糖尿病患者存在着细胞因子的过度激活，并与胰岛素抵抗密切相关，细胞因子在2型糖尿病及胰岛素抵抗的发生发展中起着重要的作用。     

Intensive insulin therapy in type 1 and type 2 diabetes

Intensive insulin regimens can produce substantial clinical benefits for patients with type 1 and type 2 diabetes, but they are associated with an increased incidence of hypoglycaemia. This article discusses such regimens and whether the risk of hypoglycaemia can be reduced by using the new basal insulin analogue, insulin glargine.     

胰岛素抵抗及血清瘦素异常与糖尿病合并脂肪肝的关系研究

目的 探讨胰岛素抵抗及血清瘦素(leptin)及其可溶性受体(sLR)异常与2型糖尿病合并脂肪肝(DfL)之间的关系,揭示部分发病机制.方法 对196例2型糖尿病患者的临床资料进行回顾性研究,其中确诊合并脂肪肝的96例病例归为DFL组,100例不伴脂肪肝的病例归为NDFL组.对两组病例进行脂代谢及胰岛素抵抗分析,并考察...     

胰岛素抵抗及血清瘦素异常与糖尿病合并脂肪肝的关系研究

Objective To study the relations among insulin resistance,abnormality of serum leptin level soluble leptin receptor(sLR) and the development of fatty liver in type 2 diabetes mellitue (DFL), so as to detect the partial pathogenesis. Methods 196 patients with type 2 diabetes mellitus were selected to retrospective study. The DFL group consisted of 96 patients who had already developed to fatty liver, while the NDFL group included 100 patients with no fatty liver. Biochemical test and insulin resistance were analysisd, and the level of serum leptin and sLR were also examined. Results The level of blood triglyceride(TG), high density lipoprotein(HDL), very low density lipoprotein( VLDL) between two groups were all statistical differences (t = - 8.124, 4.882, - 3.576, P < 0.01). The TG, HDL and VLDL level in DFL group were (3.25 ± 1.92), (1.11 ±0.28), (1.53 ± 0.60) mmol/L respectively. There was also a statistical difference in HOMA-IR level between the two groups (t = - 4.748, P < 0.01). HOMA-IR in DFL group was (4.82± 2.94), but no statistical difference in secretive function of beta cells (t = 0.123, P > 0.05). There was statistical difference in level of serum leptin and sLR between the two groups (t = - 7.435,13.332, P < 0.01); the leptin and sLR in DFL group were (4.34± 2.05) and (1.71 ± 0.53) fig/L respectively. Meanwhile, Pearson analysis showed that the blood TG level of the DFL group was positively correlated with HOMA-IR and leptin ( r = 0.845, P< 0.01; r = 0.742, P< 0.01); serum leptin level was positively correlated with HOMA-IR level (r = 0.852, P<0.01). However, serum sLR level showed negative correlation ( r = - 0.587, P < 0.01). Conclusions Insulin resistance and abnormality serum level of leptin and sLR might be one of the important causes for DFL, while abnormal lipid metabolism might be the secondary cause for this biochemical change.     

生活方式干预对大学生2型糖尿病高危人群胰岛素抵抗的影响

探讨大学生中2型糖尿病高危人群的胰岛素抵抗、空腹血糖水平及生活方式干预效果,为提高相关人群的健康状况提供依据.方法 选取沈阳市某高校有2型糖尿病一级亲属非肥胖者40名(Ⅰ组),有2型糖尿病一级亲属合并肥胖者40名(Ⅱ组),无2型糖尿病一级亲属单纯合并肥胖者40名(Ⅲ组),无上述危险因素非肥胖健康自愿者40名(Ⅳ组),进行葡萄糖耐量(OGTr)及胰岛素释放试验,同时进行血脂水平及体质量指数、腰臀比检查,对比四组血脂水平、胰岛素抵抗水平、血糖水平等指标;进行为期1年的生活方式干预治疗,观察各临床指标的变化.结果 干预前,与健康组(Ⅳ组)比较,Ⅰ组的CH,TG,LDL-C,Glu0,Glu30,Glu60,Ins30,Ins60,Ins120,HOMA-IR,△I30/△G30均较高(P值均<0.05);Ⅱ组中除HDL-C降低外,其余指标均较高(P值均<0.05);Ⅲ组中除HDL-C降低外,BMI,WHR,CH,TG,LDL-C均较高(P值均<0.05).采取生活方式干预后,Ⅰ组除HDL-C升高外,CH,TG,LDL-C,Glu0,Glu120,Ins0,Ins120,HOMA-IR,△I30/△G30均降低,差异有统计学意义(P值均<0.05);Ⅱ组除HDL-C升高外,其余指标均降低,差异均有统计学意义(P值均<0.05);Ⅲ组除HDL-C升高外,CH,TG,LDL-C,BMI,WHR均降低,差异有统计学意义(P值均<0.05);而健康组的各项指标与干预前相比差异均无统计学意义(P值均>0.05).结论 大学生中2型糖尿病高危人群胰岛素抵抗、空腹血糖的水平均较高,规范化生活方式干预可以有效降低胰岛素抵抗、胰岛素及空腹血糖水平,延缓T2DM的发生发展.     

Serum retinol-binding protein: a link between obesity, insulin resistance, and type 2 diabetes

Insulin resistance occurs under conditions of obesity, metabolic syndrome, and type 2 diabetes. It was found to be accompanied by down-regulation of the insulin-responsive glucose transporter GLUT4. Decreased adipocyte GLUT4 caused secretion by adipocytes of the serum retinol-binding protein RBP4. Enhanced levels of serum RBP4 appeared to be the signal for the development of systemic insulin resistance both in experimental animals and in humans. In mice, increased levels of serum RBP4 led to impaired glucose uptake into skeletal muscle and increased glucose production by liver, whereas lowered serum RBP4 levels greatly enhanced insulin sensitivity. Thus, a link has been established between obesity and insulin resistance: RBP4, the vitamin A-transport protein secreted into the circulation by adipocytes.     

Effects of n-3 polyunsaturated fatty acid supplementation in pregnancy on maternal and fetal erythrocyte fatty acid composition

OBJECTIVE: The aim of this study was to assess the effects of fish oil supplementation in pregnancy on maternal erythrocyte fatty acid composition at different stages of pregnancy and in the post-partum period, and on neonatal erythrocyte fatty acid composition. DESIGN: A double-blind, randomised, placebo-controlled study. SETTING:: Subiaco, Western Australia. SUBJECTS: In all, 98 women booked for delivery at St John of God Hospital, Subiaco, were recruited from private rooms of obstetricians. In total, 83 women and their healthy full-term babies completed the study. INTERVENTION: Women received either 4 g of fish oil (n=52) (56% docosahexaenoic acid (DHA) and 28% eicosapentaenoic acid (EPA) or placebo (olive oil) (n=46) per day from 20 weeks gestation until delivery. MAIN OUTCOME MEASURES: Erythrocyte phospholipid fatty acids were measured in maternal peripheral blood at 20, 30 and 37 weeks of pregnancy and at 6 weeks post partum, and from cord blood collected at birth. RESULTS: Compared to the control group, maternal EPA and DHA were significantly higher in the fish oil group at 30 and 37 weeks gestation, and remained elevated at 6 weeks post partum (P<0.001). The proportions of n-6 polyunsaturated (arachidonic acid, 22:3n-6 and 22:4n-6) were significantly lower in the fish oil supplemented group at the same time periods (P<0.001). Similarly, the proportions of EPA and DHA were significantly higher (P<0.001), and those of n-6 polyunsaturated fatty acids arachidonic acid, 20:3n-6, 22:3n-6 and 22:4n-6 were significantly lower (P<0.001), in erythrocytes from neonates in the fish oil group, compared to those in the control group. CONCLUSION: Fish oil supplementation from 20 weeks of pregnancy until birth is an effective means of enhancing n-3 fatty acid status of both mothers and neonates. Furthermore, the changes in maternal erythrocyte fatty acid composition are retained until at least 6 weeks post partum. It is essential to assess the effects of concomitant decreases in arachidonic acid status before any dietary recommendations can be made. SPONSORSHIP: The study was supported by grants from the NH & MRC and Raine Medical Research Foundation, Australia.     

抗性淀粉干预糖尿病胰岛素抵抗的临床随机对照研究

目的观察抗性淀粉干预2型糖尿病胰岛素抵抗的作用。方法将40例患者按数字随机表法随机分为2组（A组、B组）,每组20例。采用二阶段交叉设计,第Ⅰ阶段（试验前4周）A组患者为干预组（食用抗性淀粉30g/d）,B组为对照组;第Ⅱ阶段（试验后4周）A组为对照组,B组为干预组。于每阶段的首日、末日,检测患者血糖（FBG、PBG,葡萄糖氧化酶法）、血脂（TC、TG,酶法）、血胰岛素（FINS,放射免疫法）、果糖胺（FMN,硝基四氮唑蓝还原法）,计算胰岛素敏感指数（ISI）及体质指数（BMI）,分析比较这些指标的变化。结果每阶段各检测指标首日与末日的差值,干预组分别为FBG（3．21±2．34）mmol／L、PBG（4．87±2．21）mmol／L、TC（1．14±0．94）mmol／L、TG（0．73±0．68）mmol／L、FINS（3．39±3．01）mU／L、FMN（1．12±0．64）mmol／L;对照组为FBG（-0．57±1．48）mmol／L、PBG（-0．91±2．78）mmol／L、TC（-0．03±0．61）mmol／L、TG（-0．07±0．40）mmol／L、FINS（-1．04±1．94）mU／L、FMN（0．17±0．50）mmol／L,而ISI干预组为0．62±0．33高于对照组的0．19±0．31。结论抗性淀粉具有改善2型糖尿病患者的糖、脂代谢紊乱,提高胰岛素敏感性,拮抗或减轻胰岛素抵抗的作用。     

中链甘油三酯对2型糖尿病胰岛素抵抗的影响

目的探讨中链甘油三酯（MCT）干预对2型糖尿病（T2DM）患者胰岛素抵抗的影响。方法以长链甘油三酯（LCT）为对照,将T2DM患者分为MCT组、MCT／LCT组和LCT组,在控制总能量和脂肪摄入量的基础上,连续食用100％MCT油、50％MCT油＋50％LCT油和100％LCT油3个月。在0、1．5和3个月时检测血浆空腹血糖（FPC）、空腹胰岛素（FIN）、C-肽（CP）、抵抗素（resistin）浓度及β-羟基丁酸浓度,计算胰岛素抵抗指数（HOMA-IR）、胰岛素敏感指数（QUICKI）,并提取外周血单个核细胞进行抵抗素mRNA表达的检测。结果MCT组的FPG水平在1．5个月时较基线降低（P=0．042）;MCT／LCT组的FIN水平在3个月时较基线降低（P=0．005）,在1．5和3个月时MCT／LCT组的FIN水平均低于LCT组（P=0．033,P=0．006）,在1．5个月时MCT组的FIN水平低于LCT组（P=0．020）;MCT组的CP水平在1．5和3个月时均高于基线水平（均P〈0．001）,MCT／LCT组的CP水平在3个月时高于基线水平（P=0．024）;MCT／LCT组的HOMA—IR指数在3个月时低于基线水平（P=0．021）,在1．5个月时MCT／LCT组和MCT组的HOMA-IR指数均低于LCT组（P=0．033,P=0．017）;MCT／LCT组的QUICKI指数在3个月时高于LCT组（P=0．011）。3组的B-羟基丁酸水平在1．5和3个月时差异无统计学意义（P=0．617,P=0．453）。结论在控制总能量和脂肪摄入量的基础上,用MCT取代T2DM患者膳食中50％的食用油3个月,患者的胰岛素抵抗得到改善。     

Dietary counseling to improve fat quality during pregnancy alters maternal fat intake and infant essential fatty acid status

To explore the effect of maternal dietary intervention on infant essential fatty acid (FA) status, we conducted a prospective, single-blind, randomized nutrition intervention study. At the first trimester of pregnancy, 90 women from families with a history of allergy were randomized either to receive intensive dietary counseling to modify dietary intake according to current recommendations or as controls. Infants' cord and 1-mo isolated serum phospholipid FA were identified and quantified by GC. Detectable levels of eicosatrienoic acid [ETA, 20:3(n-9)] were taken as a biochemical marker for essential FA deficiency, and the DHA sufficiency index [22:6(n-3):22:5(n-6)] and the DHA deficiency index [22:5(n-6):22:4(n-6)] were taken as markers for DHA [22:6(n-3)] status. The concentration of ETA was lower in cord blood in the intervention (I) group [median 0.64 (IQR 0.40-0.78) mg/L; 2.09 (1.31-2.54) μmol/L] than in the control (C) group [0.92 (0.54-1.20) mg/L; 3.00 (1.76-3.92) μmol/L] (P = 0.048). The proportion of ETA in total FA in the I group [0.73% (0.48-0.85%)] was lower than in the C group [0.93% (0.78-1.22%)] (P = 0.003). A higher DHA sufficiency index and lower DHA deficiency index were detected in cord blood in the I group than in the C group, although the groups did not differ in the DHA concentration or proportion of the total FA. There were no differences among groups at 1 mo for any of the variables measured. Our findings suggest a better supply of essential FA, particularly important during the period of rapid development, in infants whose mothers received dietary counseling. The results thus highlight the importance of maternal diet for child health, calling for dietary counseling for pregnant women in primary health care.     

Hepatic cholesterol and fatty acid synthesis in pregnant and fetal rats: effect of maternal dietary fat and cholestyramine.

Previous studies from this laboratory have demonstrated that 20% rather than 5% (wt/wt) safflower oil or addition of 5% (wt/wt) cholestyramine to the diet of pregnant rats leads to an increase in the activity of 3-hydroxy-3-methylglutaryl CoA reductase, the rate-limiting enzyme of cholesterol synthesis, in the fetal liver. Total cholesterol, however, was not altered in fetal plasma or liver. The effect of these diets on cholesterol and fatty acid synthesis in vivo was therefore studied in fetal and maternal liver. In fetuses of rats fed a reference nonpurified diet, rates of hepatic cholesterol and fatty acid synthesis decreased from gestation d 20 to 21. In contrast, total and active 3-hydroxy-3-methyl-glutaryl CoA reductase activity increased. Adding cholestyramine to the diet or modifying the quantity of safflower oil fed had no effect on fetal hepatic lipogenesis. Maternal hepatic cholesterol synthesis was greater in rats fed cholestyramine, whereas fatty acid synthesis was lower in the dams fed the diet containing 20% compared with 5% safflower oil. The results suggest near-term fetal liver 3-hydroxy-3-methylglutaryl CoA reductase activities do not reflect fetal cholesterol synthesis in vivo.     

2型糖尿病家系胰岛素抵抗及危险因素分析

目的 研究2型糖尿病（T2DM）家系人群的胰岛素抵抗与心血管疾病危险因素聚集的关系。方法 选取2型糖尿病家系115个。共计570人，其中268例糖尿病患者为病例组，非糖尿病一级血缘亲属302人为内对照组，健康者161人为外对照组，应用x^2检验以及二项分类Logistic回归方法。结果 3组的心血管危险因素聚集程度与胰岛素抵抗程度有关（均P〈0．05）。随着胰岛素抵抗指数（HOMA-IR）的增高，3组人群的心血管疾病危险因素聚集的风险均增加。内对照组的胰岛初期分泌功能指数的平均水平高于T2DM人群和外对照人群（P=0．018，0．000）。结论 健康人群在未发生糖尿病之前均有胰岛素抵抗，因胰岛β细胞代偿性分泌增加，故不发病；当其失代偿时．则导致糖尿病发生。胰岛素抵抗为心血管疾病危险因素聚集的基础，心血管疾病危险因素聚集则是导致家系2型糖尿病高发的原因之一。     

The effect of chromium on inflammatory markers, 1st and 2nd phase insulin secretion in type 2 diabetes

Objective

Impaired insulin sensitivity (SI) and β-cell function are the two main causes of type 2 diabetes (T2D) and are related to low-grade inflammation status. Trivalent chromium has shown to improve SI in our previous study. This might be due to the ability of decreasing interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) shown in animal studies. In the current study, we measured SI, β-cell function, and plasma levels of IL-6 and TNF-α after treatment of chromium chloride (GaCr) in T2D.

Research design and methods

Sixty-six patients were randomly assigned to the 20 g of GaCr milk powder studying group or the milk powder placebo group. Oral glucose tolerance test was performed before and after the treatment. The SI and the β-cell function were measured as well.

Results

The SI was significantly improved. At the same time, the static insulin responsivity index (Φ_s) was significantly higher after the treatment (p = 0.003). On the other hand, the dynamic insulin responsivity index (Φ_d) remained unchanged. Interestingly, a significant decrease in the IL-6 level after the treatment (p = 0.015) was noted. Although there was a trend of decreasing in TNF-α, it was not statistically significant. Finally, there was no significant correlation between the δ-IL-6, SI, and Φ_d after GaCr treatment.

Conclusions

In conclusion, other than the improvement of SI, GaCr could also improve the second phase of insulin responsivity (Φ_s) and IL-6. However, δ-IL-6 was correlated with neither δ-SI nor δ-Φ_s which indicated that the improvement of SI and Φ_s might involve mechanisms other than lower inflammatory effect.     

Insulin resistance of amino acid and protein metabolism in type 2 diabetes

Although insulin resistance in T2DM (type 2 diabetes mellitus) is usually referred to glucose and lipid metabolism, the question whether such a resistance affects also amino acid and protein metabolism is both relevant and not easy to be answered. Available data indicate a reduced response to insulin in the inhibition of proteolysis at low, near basal hormone levels, whereas such a response appears to be normal at high physiological doses. In most studies in T2DM subjects the stimulation of whole-body protein synthesis in the presence of hyperinsulinemia and euaminoacidemia appears to be normal, although one single study reported lower rates in male T2DM subjects with obesity. The response to insulin of plasma protein synthesis (albumin and fibrinogen) is also normal. However, some metabolic steps of amino acids related to vascular complications (methionine and arginine) exhibit a defective response to insulin in T2DM subjects with nephropathy. In summary, although gross alterations in the response of whole-body protein turnover are not evident in T2DM, specific investigations reveal subtle abnormalities in metabolic steps of selected amino acids. Furthermore, the effects of interaction between diabetes (with the associated insulin resistance) and older age in the pathogenesis of sarcopenia in the elderly deserve more specific studies.     

Suppression of nocturnal fatty acid concentrations by bedtime carbohydrate supplement in type 2 diabetes: effects on insulin sensitivity, lipids, and glycemic control

BACKGROUND: Bedtime ingestion of slow-release carbohydrates leads to sustained nocturnal fatty acid suppression and improved glucose tolerance in type 2 diabetic patients. OBJECTIVE: This study assessed the effects of 2 different doses of bedtime carbohydrate supplement (BCS) on morning glycemic control and glycated hemoglobin (Hb A(1c)) in type 2 diabetic patients. In addition, the effects of the high-dose BCS on insulin sensitivity and postprandial glucose and triacylglycerol concentrations were assessed. DESIGN: Two BCS doses were studied separately in 7-wk randomized, placebo-controlled, double-blind studies with either a parallel (low-dose BCS; n = 24 patients) or crossover (high-dose BCS; n = 14 patients) design. The effects of the low and high doses (0.30 and 0.55 g uncooked cornstarch/kg body wt, respectively) were compared with those of a starch-free placebo. RESULTS: Compared with the starch-free placebo, the high-dose BCS ( approximately 45 g) produced enhanced nocturnal glucose (P < 0.01) and insulin (P < 0.01) concentrations as well as a 32% suppression of fatty acid concentrations (P < 0.01). Moreover, glucose tolerance (P < 0.05) and C-peptide response (P < 0.05) improved after breakfast the next morning. The low-dose BCS ( approximately 25 g) improved fasting blood glucose concentrations (P < 0.05). However, there were no improvements in insulin sensitivity, postprandial triacylglycerol concentrations, or Hb A(1c) after 7 wk. CONCLUSION: Nocturnal fatty acid suppression by BCS improved fasting and postprandial blood glucose concentrations in type 2 diabetic patients the next morning. In contrast, no improvements in insulin sensitivity, postprandial triacylglycerol concentrations, or long-term glycemic control assessed by Hb A(1c) were seen after BCS supplementation.     

Enhanced Na-Li countertransport: a marker of inherited susceptibility to type 2 diabetes

Introduction The association between type 2 diabetes and hypertension has long been described, but the mechanisms remain unclear. Na-Li countertransport (Na-Li CT) activity is viewed as a marker of inherited pre-disposition to hypertension, especially if associated with other metabolic abnormalities. Aim To evaluate whether enhanced Na-Li CT activity is a predictor of type 2 diabetes. METHODS: Study participants were 2167 men and women, 30-70 years. Na-Li CT activity, glucose, HDL cholesterol, blood pressure, height, and weight were measured. Six years incidence of diabetes (WHO) was assessed. RESULTS: Baseline Na-Li CT activity was significantly higher for people who developed diabetes at follow-up (n = 101) than for those who remained non-diabetic (364 +/- 184 vs 300 +/- 150 micromol/l RBC/h, P < 0.001). This finding was confirmed after correction for obesity, hypertension, and blood glucose. Six years' incidence of diabetes increased across tertiles of baseline Na-Li CT activity--from 2 to 7%--with a significant linear trend (P < 0.001). In multivariate analyses Na-Li CT is a significant predictor of diabetes independent of age, BMI, HDL cholesterol, hypertension, and plasma glucose; based on exponentiation of the regression coefficient Na-Li CT higher by 154 micromol (i.e. 1 SD of the population mean) was associated with a 36% greater risk of incident diabetes. CONCLUSIONS: Prospective data from the present study show for the first time enhanced Na-Li CT activity is a significant predictor of development of diabetes in adults, thus suggesting that it could be viewed as a pre-clinical, possibly genetic, marker of inherited susceptibility to type 2 diabetes.