| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Center for Human Nutrition and the Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390
Address all correspondence and requests for reprints to: Nicola Abate, M.D., University of Texas Southwestern Medical Center, 6011 Harry Hines Boulevard, Dallas, Texas 75390-9169. E-mail: nicola.abate{at}utsouthwestern.edu.
 |
Abstract |
|---|
 Top Abstract IntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
|
Introduction |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
One potential mechanism for insulin resistance may be genetic defects that impair the insulin-signaling pathway. Several candidate genes for defects in insulin signaling have been postulated, and a few studies report positive associations between polymorphisms of genes in the insulin-signaling pathway and insulin resistance (25). Two of the latter are insulin receptor substrate-1 (IRS-1) G972A (26, 27, 28, 29) and plasma cell membrane glycoprotein (PC-1) K121Q (30, 31, 32, 33, 34, 35, 36, 37, 38, 39). The present study was carried out to determine whether these two polymorphisms contribute to the ethnic susceptibility to insulin resistance of Asian Indians. To accomplish this goal we assessed the frequency of IRS-1 G972A and PC-1 K121Q in Asian Indians and Caucasians. In addition, insulin responsiveness to an oral glucose load and glucose disposal rates during euglycemic hyperinsulinemia (insulin sensitivity index) were measured in subjects with IRS-1 G972A and PC-1 K121Q vs. wild-type in these two populations.
|
Subjects and Methods |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
To determine whether the frequencies of the two candidate genetic polymorphisms were different in the two ethnic groups, we first recruited Asian Indians and Caucasians by public advertisement and offering free screening for cardiovascular risk factors at University of Texas Southwestern Lipid and Heart Disease Risk Management Clinic (Dallas, TX). Informed consent was obtained from all participants. The study was approved by the institutional review board at University of Texas Southwestern Medical Center (Dallas, TX). Each of these participants was administered a health questionnaire. Personal and family history of coronary artery disease included any history of angina, myocardial infarction, and bypass surgery. Height and weight were measured by standard procedures. Blood pressure was measured after about 5 min of rest in the sitting position, using an automated sphygmomanometer. A blood sample was then drawn from each participant and immediately refrigerated. After separation of plasma and serum, aliquots were frozen at -80 C. Blood samples were collected for biochemistries and genetic studies. To further evaluate the impact of the studied mutations on insulin resistance, we invited the volunteers to participate in the second part of the study, which included more detailed anthropometric measurements (skinfolds, waist and hip circumferences, and underwater weighing) and an oral glucose tolerance test (OGTT). To further explore the role of genetics on insulin resistance, we invited young individuals (<40 yr of age) to have hyperinsulinemic-euglycemic clamps as well.
A total of 1376 subjects volunteered for the first part of the study. Of those, 638 originated from the Asian Indian subcontinent (India, Pakistan, and Bangladesh), and 738 subjects were of European ancestry. The Asian Indian group included both subjects who had recently immigrated to U.S. and those who were born in U.S. In Table 1
the general characteristics of Asian Indians and Caucasians are compared. The 2 ethnic groups had similar ratios of male to female participants, but the percentage of menopausal women was lower in the Asian Indian group, probably as a reflection of their younger age. Despite lower average age and body mass index, systolic blood pressure, diastolic blood pressure, and fasting plasma insulin concentrations were significantly higher in the Asian Indians compared with the Caucasians. Plasma concentrations of total cholesterol and low (LDL) and high (HDL) density lipoprotein cholesterol were significantly lower in the Asian Indians, whereas plasma triglycerides concentrations were higher. Personal and family histories in the 2 ethnic groups are compared in Table 2. The Asian Indians had twice the prevalence of personal history for diabetes mellitus as the Caucasians (P = 0.01). The family history of coronary artery disease was significantly lower in the Asian Indians (P < 0.0001). The data on family history were obtained by each subject’s recall. It is unclear why a lower frequency of coronary artery disease was detected in the Asian Indians despite higher family history of diabetes mellitus. A similar frequency of smoking and the remainder of personal and family history were reported in the 2 ethnic groups.
|
|
Body composition studies
All participants in the OGTT and clamp studies had anthropometric measurements made during admission at the GCRC. Waist and hip circumferences were measured, using a flexible measuring tape with a tension caliper at the extremity (Gulick-creative Health Product, Inc., Plymouth, MI), midway between xyphoid and umbilicus during the midexpiratory phase, and at the maximum circumference in the hip area, respectively. Skin folds thickness was measured at nine different anatomical sites (subscapular diagonal and vertical, chest, midaxillary, abdominal horizontal and vertical, suprailiac diagonal and vertical, triceps, biceps, thigh, and calf) using a Lange skinfold caliper (Cambridge Scientific Instruments, Inc., Cambridge, MD), as previously reported (12). Body density was calculated from measurements of body volume determined by hydrostatic weighing, with adjustment for residual volume measured by helium dilution during the underwater weighing. Percent body fat was calculated using the Siri equation (40), assuming a fat-free density of 1.10 g/cc for men and 1.097 g/cc for women.
Glucose tolerance testing
A standard oral glucose tolerance test with 75 g glucose (Tru-Glu100, Fisher Scientific, Pittsburgh, PA) was conducted after 12-h overnight fasting. An iv catheter was placed in a forearm vein, and blood was collected for determination of glucose and insulin concentrations before glucose administration and at 30-min intervals thereafter for 180 min.
Hyperinsulinemic-euglycemic clamps
On the morning of study d 4, breakfast was withheld, and the euglycemic-hyperinsulinemic clamp procedure was performed after an overnight fast. Two polyethylene catheters were placed under local anesthesia. One catheter was placed in a dorsal hand vein for blood sampling, and the hand was kept in a heated box at 70 C for arterialization of venous blood. At 0800 h, a primed-continuous infusion of regular insulin (Humulin, Squibb-Novo, Princeton, NJ) was started at a rate of 80 mU/m2 (body surface area)·min and continued for 2 h. The insulin infusion rate of 80 mU/m2·min is expected to assure complete suppression of hepatic glucose output during the hyperinsulinemic phase of study. A 20% glucose infusion was started after 4 min of insulin infusion at a rate calculated to maintain the plasma glucose concentration at the fasting level throughout the clamp procedure, according to the method described by DeFronzo et al. (41). Blood for plasma glucose concentration measurements was drawn every 5 min for the entire duration of the study. Blood for the determination of insulin levels was drawn every 10 min from -30 to 0 min (baseline phase) and from 80–120 min (hyperinsulinemic phase, after 80 min of equilibration time).
The rate of glucose infusion was calculated based on glucose concentration obtained at various times during the clamp study. The rate of glucose disposal (Rd) was calculated by subtracting the urinary glucose excretion from the rate of glucose appearance and using space correction. The Rd data were computed in milligrams per minute per kilogram of lean body mass. To account for differences in plasma insulin levels during hyperinsulinemia, the insulin sensitivity index was obtained for the study groups by dividing Rd by plasma insulin concentrations in milliunits per milliliter x 100.
Biochemistries
Cholesterol and triglycerides were measured with enzymatic methods. Very low density lipoprotein (VLDL; density, <1.006 g/ml) was removed by preparative ultracentrifugation, and cholesterol was measured in the VLDL fraction and infranatant. HDL cholesterol was determined in the supernatant after precipitating apolipoprotein B-containing lipoproteins using heparin-manganese chloride. LDL cholesterol was calculated as the difference between the cholesterol content of the 1.006 g/ml infranatant and HDL cholesterol. Insulin was measured by RIA at Linco Research, Inc. (St. Charles, MO).
DNA amplification by PCR
Fasting blood samples were drawn into a 10-ml vacuum tube containing EDTA. Plasma was separated by centrifugation and stored at 4 C until analysis. Genomic DNA was isolated from whole blood using commercial DNA isolation kits from Qiagen (Chatsworth, CA). The genomic DNA of each subject was amplified in a final volume of 10 µl containing 50 mM KCl, 10 mM Tris (pH 8.3), 1.5 mM MgCl2, 75 ng of each primer, 100 µM deoxy-NTP, and 1 U Taq polymerase.
Assay of PC-1 and IRS-1 polymorphisms
PC-1 and IRS-1 polymorphisms were detected by PCR-restriction fragment length polymorphism analysis. The PC-1 K121Q polymorphism creates an AvaII restriction site (5'-GGACC-3'). To assay this polymorphism, a 238-bp fragment encompassing the region of interest was amplified by PCR using oligonucleotides 5'-CTGTGTTCACTTTGGACATGTTG-3' and 5'-GACGTTGGAAGATACCAGGTTG-3'. The PCR-amplified DNA fragment was digested by adding 10 U AvaII restriction enzyme in 30 µl buffer 4 (New England BioLabs, Inc., Beverly, MA) to the PCR product, and then it was run on a 2% agarose gel. The K alleles are displayed as a single uncut band of 238 bp, whereas the Q alleles are shown as a doublet of 148- and 90-bp bands. The IRS-1 G972A polymorphism creates an SmaI restriction site (5'-CCCGGG-3'). To assay the IRS-1 G972 polymorphism, a 200-bp fragment was PCR-amplified using the primers 5'-CTTTCCACAGCTCACCTTCTGTCA-3' and 5'-CCGGGTAGGCCTGCAAATGCTAGC-3'. Digestion was obtained by adding 10 U SmaI in 30 µl buffer 4 (New England Biolabs, Inc.) to the PCR product. The digestion products were then run on a 2% agarose gel.
Statistical analysis
Continuous demographic variables were compared between Asian Indians and Caucasians using the Mann-Whitney U test. The frequencies of mutations and of personal or family history variables were compared between ethnic groups using Fisher’s exact test. Two-way ANOVA models were used to assess the effects of ethnicity, polymorphisms, and the interaction between ethnic group and polymorphisms. Multiple comparisons of these group means were made with the least squares contrasts of the ANOVA models. Due to skewness, triglycerides were log-transformed before analysis. Statistical analysis was performed using SAS version 8.02 (SAS Institute, Inc., Cary, NC).
|
Results |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
Thirty-three percent of Asian Indians had at least one copy of PC-1 121Q; the frequency in Caucasians was significantly less at 27% (Fig. 1). The prevalence of carrying at least one copy of IRS-1 972A was much lower (6% in Asian Indians and 7% in Caucasians). There were 3% of Asian Indians and 2% of Caucasians with homozygosity of the PC-1 121 Q polymorphism. The allele frequency of PC-1 121Q was 14.3% in the Caucasian group and 17.9% in the Asian Indian group (by 
2, P = 0.01). The results are in Hardy-Weinberg equilibrium. Individuals homozygous and heterozygous for PC-1 121Q were grouped together for analysis and identified as a study subgroup carrying the PC-1 121Q variant. Similarly, individuals homozygous and heterozygous for IRS-1 972A were grouped together for analysis.
|
A total of 158 Asian Indians and 152 Caucasians underwent OGTT (Tables 3 and 4). Although the 2 groups were of similar age and body mass index, Asian Indians generally had a higher thickness of truncal skin folds than Caucasians. Systolic blood pressure tended to be lower in Asian Indians. Figure 2 depicts the changes in plasma glucose and plasma insulin concentrations during OGTT and the overall glucose and insulin area under the curve (AUC) during the OGTT. Plasma glucose concentrations and glucose AUC were similar during the OGTT for the 4 subgroups. The plasma insulin AUC was higher for the Asian Indians as a group than for Caucasians. However, the most striking difference was present in Asian Indians with PC-1 121Q variant. In this subgroup, the insulin AUC was strikingly higher than in the subjects with wild-type PC-1. In contrast, although statistically different, the insulin AUC was only marginally higher in Asian Indians with wild-type PC-1 than in Caucasians. Of interest, no difference was found between Caucasians subgroups with the PC-1 121Q variant and PC-1 wild-type. The IRS-1 polymorphism was not associated with any difference in either glucose AUC or insulin AUC during the OGTT among any of the study subgroups (data not shown).
|
|
|
Clamp studies were carried out in 23 Asian Indians, including 15 men and 3 women with wild-type PC-1 and 5 men with the 121Q variant. Plasma glucose levels were comparable between the 2 subgroups both at baseline [88 ± 4 mg/dl (4.9 ± 0.2 mmol/liter) and 88 ± 11 mg/dl (4.9 ± 0.06 mmol/liter), respectively] and during hyperinsulinemia [88 ± 4 mg/dl (4.9 ± 0.2 mmol/liter) and 86 ± 4 mg/dl (4.8 ± 0.2 mmol/liter), respectively]. On the other hand, baseline insulin and insulin concentrations during the last 40 min of the clamps were significantly higher in Asian Indians carrying the PC-1 121Q variant [200 ± 34 µU/ml (1389 ± 236 pmol/liter)] compared with those in Asian Indians with the wild-type PC-1 [167 ± 21 µU/ml (1160 ± 146 pmol/liter)]. There were no differences among any of the parameters listed in Tables 3
and 4 for the 2 subgroups selected for glucose clamp studies (data not shown). In those subjects with PC-1 121Q, insulin sensitivity was significantly reduced compared with that in subjects with wild-type PC-1 (Fig. 3).
|
and 4. Moreover, the difference in insulin sensitivity index was not statistically significant between the 2 subgroups (Fig. 3), nor was the insulin sensitivity index for Asian Indians with wild-type PC-1 different from that for the Caucasian subgroups. Finally, the IRS-1 polymorphism was not associated with any difference in insulin sensitivity index among the study subgroups (data not shown). |
Discussion |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
If the PC-1 121Q allele associates with insulin resistance and confers increased risk for type 2 diabetes, it is of importance to determine the frequency of this polymorphism in various populations and the associated risk for type 2 diabetes. Previous studies in Caucasian subjects revealed a variable allele frequency in different populations. The lowest prevalences (9.8% and 10.5%) were reported in two unrelated nondiabetic Finnish groups by Kubszek et al. (43). Another study that included Finnish and Swedish subjects (42) reported a PC-1 121Q allele frequency of 13.8%, very similar to the 14% reported in Spanish subjects (44). Pizzuti et al. (30) reported the highest PC-1 121Q allele frequency in a Sicilian population sample (17.8%). The finding of a PC-1 121Q allele frequency of 14.3 in the Caucasians of our study is consistent with the reported allele frequency in the European population. Interestingly, we detected a significantly higher PC-1 121Q allele frequency in our Asian Indian population. The allele frequency of 17.9% in Asian Indians is comparable to the reported frequency in the Sicilian population (30), which also manifests a strong association between PC-1 121Q and insulin resistance.
In the current study, Caucasians from our geographical region with the PC-1 121Q variant revealed no evidence of increased insulin resistance compared with the control group with wild-type PC-1. In previous reports, the finding of a positive association between PC-1 121Q and insulin resistance in other Caucasian populations has been inconsistent. Positive associations have been reported by Pizzutti et al. (30) and Frittitta et al. (31) for Sicilians, by Gu et al. (42) in intrafamily association studies in subjects from Finland and Sweden, and by Kubaszek et al. (43) in Finnish subjects. In contrast, Rasmussen et al. (45) and Gonzalez-Sanchez et al. (44) found no association among Danish and Spanish Caucasians, respectively.
The results of our study do not elucidate the reasons for the observed differences in allele frequencies of PC-1 121Q between Asian Indians and Caucasians or the molecular basis for the positive association between PC-1 121Q and insulin resistance in Asian Indians, but not in some Caucasian groups. Whether the difference in frequencies of the polymorphism is present in the whole South Asian population and the whole Caucasian population is unknown. Both Asian Indian and Caucasians in this study were samples of convenience and cannot be considered representative of the whole population. However, the difference in frequency is suggestive enough to justify a more extensive study and more representative sampling.
There is little doubt that Asian Indians as a group are more insulin resistant than Caucasians. This difference has been documented in several studies (14, 15, 46) and is consistent with a high prevalence of type 2 diabetes throughout India and in migrant Indians (16, 17, 18, 19). These findings suggest that insulin resistance in Asian Indians has a strong genetic component. If so, Asian Indians could have a combination of independent genes, each affecting insulin sensitivity. Alternatively, there could be multiple interacting genes that are required to produce a high prevalence of insulin resistance. We cannot rule out the possibility that migrant Indians may not be representative of the whole South Asian population with respect to gene clustering. Migration may be more likely to occur in certain segments of the population, which could differ in genetic architecture from other segments. If so, the group prone to migration may be enriched in certain genetic patterns that influence insulin sensitivity. In the current study, details of immigrant status in the Asian Indian cohort, including recent vs. first generation and length of stay in the United States, were not documented sufficiently to draw a firm conclusion. Thus, replication of the current findings in different regions of the Indian subcontinent will be necessary to define the scope of the association between PC-1 121Q variant and insulin resistance in all Asian Indians.
A perplexing observation is the failure to observe an association between PC-1 121Q and insulin resistance in some Caucasian populations (44, 45). This failure raises the possibility that the positive association in Asian Indians is spurious. However, several findings support a true association. Positive associations have been reported in other Caucasian cohorts (30, 31, 42, 43) and were independently confirmed by both OGTT and glucose clamp studies in current Asian Indians. If the association is real, it still does not prove that PC-1 121Q per se can cause insulin resistance. It could be an associated marker for a particular genetic architecture that is responsible for insulin resistance. Such a genetic marker might occur in some populations, but not in others. Alternatively, PC-1 121Q acting alone may not be responsible for insulin resistance, but may interact with one or more other genes that are required to produce detectable insulin resistance. In our view this latter possibility seems the more likely mechanism to explain the inconsistent relationship between PC-1 121Q and insulin resistance in different populations.
The results of our study suggest that the PC-1 121Q polymorphism is a key factor for the development of insulin resistance in Asian Indians even if it does not act alone. Of interest, plasma AUCs during OGTT and insulin sensitivity indexes in Asian Indian PC-1 wild types were not different from those in Caucasians. Our study used two different techniques to assess insulin resistance: measurement of the insulin AUC of an OGTT and measurement of Rd during a hyperinsulinemic-euglycemic clamp. Although a smaller number of subjects participated in the clamp studies, the findings from the OGTT on a much larger sample size were virtually identical those from the clamps. However, before it can be concluded that the PC-1 121Q variant is a dominant factor associated with insulin resistance in Asian Indians, the study would have to be greatly expanded to include a larger number of study participants in the hyperinsulinemic-euglycemic clamps. Given the relatively low and unequal prevalence of PC-1 121Q in different ethnic groups, future investigations should be designed to assure equal distribution of PC-1 subgroups within the clamp studies. In addition, to attempt a relative quantification of the impact of the PC-1 121Q polymorphism on the excessive insulin resistance of Asian Indians, more detailed information about environmental factors involved in the pathogenesis of insulin resistance is needed. It seems unlikely that a single polymorphism in one gene can entirely explain the propensity of South Asians to insulin resistance. Nonetheless, it is of interest that the frequency of the PC-1 121Q variant is higher among Asian Indians than Caucasians. This finding raises the possibility that PC-1 121Q confers a biological advantage, such as that postulated in the thrifty gene hypothesis (47).
Of interest are the results we obtained on IRS-1 972A. This polymorphism has also been associated with insulin resistance in previous studies (26, 27). However, the prevalence of the IRS-1 972A variant has been reported to be very low in the Caucasian population (48). Pima Indians, another ethnic group with excessive insulin resistance, have been shown not to have excessive prevalence of the IRS-1 972A mutation (28). The lack of association between the prevalence of IRS-1 972A polymorphisms and the prevalence of diabetes has been shown in both Caucasian and Asian Indian populations (29). Our findings confirm the low prevalence of this polymorphism in nondiabetic Caucasians and Asian Indians. Furthermore, we found no relationship between IRS-1 972A and excessive insulin resistance in the Asian Indian population. Although not all ethnic groups have been studied, the low prevalence of the mutation and the absence of an ethnic difference in prevalence suggest that the IRS-1 G972A polymorphism is unlikely to play a major role in the interethnic variability in insulin resistance susceptibility.
In summary, we conclude that PC-1 121Q polymorphism associates strongly with primary insulin resistance in Asian Indians and significantly contributes to the insulin resistance susceptibility of this population. Insulin resistance is almost certainly the result of a complex interaction of environmental/acquired factors and genetic factors. Obesity, fat distribution, and physical activity are related to insulin resistance, and they influence the variability of insulin sensitivity in the population. Nonetheless, identification of individuals who are genetically susceptible to insulin resistance may provide a useful tool for intervention strategies to reduce the risk for type 2 diabetes and cardiovascular disease in our population.
|
Acknowledgments |
|---|
|
Footnotes |
|---|
Abbreviations: AUC, Area under the curve; CHD, coronary heart disease; GCRC, General Clinical Research Center; HDL, high density lipoprotein; IRS, insulin receptor substrate; LDL, low density lipoprotein; OGTT, oral glucose tolerance test; PC-1, plasma cell membrane glycoprotein; Rd, rate of glucose disposal; VLDL, very low density lipoprotein.
Received March 13, 2003.
Accepted August 21, 2003.
|
References |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
Arg972 amino acid polymorphism in insulin receptor substrate-1 affects glucose metabolism in skeletal muscle cells. J Clin Endocrinol Metab 85:2004–2013
-subunit. Diabetes 49:13–19[Abstract]
gene expression, is associated with a reduction of both whole body insulin sensitivity and insulin receptor tyrosine-kinase activity. Diabetologia 40:282–289[CrossRef][Medline]
This article has been cited by other articles:
 |
|
 |
|
  E. S. Stolerman, A. K. Manning, J. B. McAteer, J. Dupuis, C. S. Fox, L. A. Cupples, J. B. Meigs, and J. C. Florez Haplotype Structure of the ENPP1 Gene and Nominal Association of the K121Q Missense Single Nucleotide Polymorphism With Glycemic Traits in the Framingham Heart Study Diabetes, July 1, 2008; 57(7): 1971 - 1977. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. D. Goldfine, B. A. Maddux, J. F. Youngren, G. Reaven, D. Accili, V. Trischitta, R. Vigneri, and L. Frittitta The Role of Membrane Glycoprotein Plasma Cell Antigen 1/Ectonucleotide Pyrophosphatase Phosphodiesterase 1 in the Pathogenesis of Insulin Resistance and Related Abnormalities Endocr. Rev., February 1, 2008; 29(1): 62 - 75. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Eller, K. Hochegger, G. M. Feuchtner, E. Zitt, I. Tancevski, A. Ritsch, F. Kronenberg, A. R. Rosenkranz, J. R. Patsch, and G. Mayer Impact of ENPP1 genotype on arterial calcification in patients with end-stage renal failure Nephrol. Dial. Transplant., January 1, 2008; 23(1): 321 - 327. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. Willer, L. L. Bonnycastle, K. N. Conneely, W. L. Duren, A. U. Jackson, L. J. Scott, N. Narisu, P. S. Chines, A. Skol, H. M. Stringham, et al. Screening of 134 Single Nucleotide Polymorphisms (SNPs) Previously Associated With Type 2 Diabetes Replicates Association With 12 SNPs in Nine Genes Diabetes, January 1, 2007; 56(1): 256 - 264. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Bottcher, A. Korner, T. Reinehr, B. Enigk, W. Kiess, M. Stumvoll, and P. Kovacs ENPP1 Variants and Haplotypes Predispose to Early Onset Obesity and Impaired Glucose and Insulin Metabolism in German Obese Children J. Clin. Endocrinol. Metab., December 1, 2006; 91(12): 4948 - 4952. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Freeman and R.D. Cox Type-2 diabetes: a cocktail of genetic discovery Hum. Mol. Genet., October 15, 2006; 15(suppl_2): R202 - R209. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Bochenski, G. Placha, K. Wanic, M. Malecki, J. Sieradzki, J. H. Warram, and A. S. Krolewski New Polymorphism of ENPP1 (PC-1) Is Associated With Increased Risk of Type 2 Diabetes Among Obese Individuals Diabetes, September 1, 2006; 55(9): 2626 - 2630. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Radha, K. S. Vimaleswaran, H. N. S. Babu, N. Abate, M. Chandalia, P. Satija, S. M. Grundy, S. Ghosh, P. P. Majumder, R. Deepa, et al. Role of Genetic Polymorphism Peroxisome Proliferator-Activated Receptor-{gamma}2 Pro12Ala on Ethnic Susceptibility to Diabetes in South-Asian and Caucasian Subjects: Evidence for heterogeneity Diabetes Care, May 1, 2006; 29(5): 1046 - 1051. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. T. Bloomgarden 2nd International Symposium on Triglycerides and HDL: Metabolic syndrome Diabetes Care, October 1, 2005; 28(10): 2577 - 2584. [Full Text] [PDF]
|
|
|
|
|
|
S. Bacci, O. Ludovico, S. Prudente, Y.-Y. Zhang, R. Di Paola, D. Mangiacotti, A. Rauseo, D. Nolan, J. Duffy, G. Fini, et al. The K121Q Polymorphism of the ENPP1/PC-1 Gene Is Associated With Insulin Resistance/Atherogenic Phenotypes, Including Earlier Onset of Type 2 Diabetes and Myocardial Infarction Diabetes, October 1, 2005; 54(10): 3021 - 3025. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Abate, M. Chandalia, P. Satija, B. Adams-Huet, S. M. Grundy, S. Sandeep, V. Radha, R. Deepa, and V. Mohan ENPP1/PC-1 K121Q Polymorphism and Genetic Susceptibility to Type 2 Diabetes Diabetes, April 1, 2005; 54(4): 1207 - 1213. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
, P < 0.0001 for mean difference between Asian Indians with the PC-1 121Q variant and Caucasians with the PC-1 121Q variant. 
, P = 0.02 for mean difference between Asian Indians with wild-type PC-1 and Caucasians with wild-type PC-1. The Systeme International conversion factor is 0.0555 pmol/liter for glucose and 0.695 pmol/liter for insulin.