β-Cell Function and Insulin Sensitivity in Normal Glucose-Tolerant Subjects Stratified by 1-Hour Plasma Glucose Values

Abstract

Aim:

This study was designed to assess β-cell function and insulin sensitivity indices among normal glucose tolerance (NGT) subjects stratified by 1-h plasma glucose (1hPG) values during an oral glucose tolerance test (OGTT).

Materials and Methods:

One hundred sixty-six NGT subjects underwent a five-point OGTT, and glucose and insulin levels were estimated. We calculated the following indices: (a) β-cell function (homeostasis assessment model—β-cell function [HOMA-β] and Insulinogenic Index [IGI]) and (b) insulin sensitivity (homeostasis assessment model—insulin resistance [HOMA-IR], Matsuda Index, and Insulin Sensitivity Index [ISI]).

Results:

NGT subgroups with elevated 1hPG values (i.e., 1hPG ≥143 to <155 mg/dL and 1hPG ≥155 mg/dL) did not differ from those with 1hPG <143 mg/dL by HOMA-β (P = 0.236) but had significantly lower IGIs (367 ± 239 vs. 257 ± 243 vs. 246 ± 239; P = 0.019). With respect to ISIs, HOMA-IR was not significantly different among the groups (P = 0.103). However, the Matsuda Index (11.2 ± 5.0 vs. 7.4 ± 4.8 vs. 5.5 ± 4.9; P < 0.001) and ISI (0.015 ± 0.010 vs. 0.012 ± 0.006 vs. 0.011 ± 0.011; P = 0.028) were significantly lower in subjects with elevated 1hPG values.

Conclusions:

NGT subjects with elevated 1hPG levels have alterations in β-cell function and insulin sensitivity compared with those with normal 1hPG levels.

Introduction

Normal glucose tolerance (NGT) is defined as fasting plasma glucose (FPG) of <100 mg/dL and 2-h plasma glucose (2hPG) of <140 mg/dL. In the natural history of individuals with type 2 diabetes mellitus (T2DM) in the stage of NGT, progression occurs to dysglycemia (i.e., the stage of prediabetes [i.e. impaired fasting glucose or impaired glucose tolerance]) and later to full-blown T2DM.^1,2 However, although some individuals with NGT progress, others remain at the NGT stage, highlighting the need to identify the subgroups of NGT who are at increased risk of progression to dysglycemia.³

There is increasing evidence that among NGT subjects, those with raised 1-h plasma glucose (1hPG) values tend to progress to dysglycemia.^4

–8 We recently reported a study of 1,179 NGT individuals, of whom 392 (33.2%) developed prediabetes and 148 (12.6%) developed diabetes (i.e., overall, 45.8% developed dysglycemia) during a follow-up period of 13 years.⁴ We thus confirmed, as found in earlier studies, that NGT subjects with elevated 1hPG values progressed to prediabetes and diabetes and also showed that the rate of progression was faster.⁴ Using receiver operator curves we showed that among NGT subjects, a 1hPG predictive cutoff of ≥143 to <155 mg/dL predicted development of prediabetes, whereas values of ≥155 mg/dL predicted progression to diabetes.⁴

The present study aimed at studying markers of β-cell function and insulin sensitivity⁹ in NGT subjects stratified by these 1hPG cut points using various glucose and insulin indices.

Materials and Methods

The study group comprised 166 individuals with NGT (defined as FPG level of <100 mg/dL [5.6 mmol/L] and 2hPG level of <140 mg/dL [7.8 mmol/L]). Subjects were 10–48 years of age seen at a specialized diabetes center in Chennai in south India. Written informed consent was obtained from all participants before they were included in the study. All human rights were observed in keeping with Declaration of Helsinki 2008 (ICH GCP) and the Indian Council of Medical Research guidelines. The study was approved by the Institutional Ethical Committee of the Madras Diabetes Research Foundation.

A questionnaire elicited data on age, gender, and family history of diabetes. Anthropometric measurements (height, weight, and waist circumference) and systolic and diastolic blood pressures were recorded. Body mass index (in kg/m²) was calculated using the following expression: weight (in kg) divided by height square (in m²).

A 75-g oral glucose tolerance test (OGTT) was carried out in all subjects. A fasting venous sample was drawn following an overnight fast of at least 10 h. Subjects were immediately asked to consume 82.5 g of oral glucose (Glucon D; Heinz, Mumbai, India) (equivalent to 75 g of anhydrous glucose) dissolved in 200 mL of water, and they consumed the drink within a period of 5 min. Glucose (in mg/dL) and insulin (in pmol/L) levels were measured from blood samples drawn at 0, 30, 60, 90, and 120 min. Insulin was converted from units of μlU/mL to pmol/L using the conversion factor 6.945, and glucose was converted from units of mg/dL to mmol/L by dividing by 18 where required when calculating the insulin secretory and insulin sensitivity indices. Glycated hemoglobin and lipid level estimations were also performed.

All the blood samples were analyzed at the clinical laboratory of our Center, which is accredited by the College of American Pathologists and the National Accreditation of Biological Labs of the Government of India. Plasma glucose was measured using the Hitachi-912 autoanalyzer (Roche Diagnostics GmbH, Mannheim, Germany) using kits (hexokinase method) supplied by Roche Diagnostics GmbH. Serum cholesterol (cholesterol oxidase–peroxidase–amidopyrine method) and serum triglycerides (glycerol phosphate oxidase–peroxidase–amidopyrine method) were measured using the Hitachi-912 autoanalyzer. Low-density lipoprotein cholesterol was calculated using the Friedewald formula.¹⁰ Serum insulin concentration was estimated using the electrochemiluminescence method (COBAS E411 analyzer; Roche Diagnostics). Glycated hemoglobin was measured using high-performance liquid chromatography with the Bio-Rad (Hercules, CA) Variant™ II Turbo machine. The intra- and interassay coefficients of variation for the biochemical assays ranged from 3.1% to 7.6%. NGT subjects were stratified by 1hPG: 1hPG <143 mg/dL, 1hPG ≥143 to <155 mg/dL, and 1hPG ≥155 mg/dL.⁴

The following indices were used to assess β-cell function and insulin sensitivity:

β-Cell function

• Homeostasis model assessment—β-cell function (HOMA-β),^9,11,12 defined as HOMA-β = (fasting plasma insulin [μU/mL] × 20)/(FPG [mmol/L] – 3.5)^11,12

• Insulinogenic Index (IGI), defined as the ratio of difference in fasting to 30-min insulin to glucose values = (ΔI _0–30/ΔG _0–30)^13
–15

Insulin sensitivity

• Homeostasis assessment model—insulin resistance (HOMA-IR), defined as HOMA-IR = ([FPG (mmol/L) × fasting plasma insulin (μIU/mL)]/22.5)^9,11,12

• Insulin Sensitivity Index (ISI), estimated as (1/fasting plasma insulin [pmol/L])^9,11,12

• Matsuda Index, defined as (10,000/square root of [fasting glucose × fasting insulin] × [mean glucose × mean insulin]). Mean glucose and mean insulin for the Matsuda Index were calculated from values at 0, 30, 60, 90, and 120 min of the OGTT.¹⁶

Statistical analysis

Sample size calculation was carried out based on the prevalence of glucose intolerance of 45.8% (95% confidence interval, 36.6–55) with precision set at 20% of the lower limit of the 95% confidence interval, and a sample size of 155 was determined.⁴ The sample size was increased to 166 to account for possible non-responders. Data on all 166 subjects were included in the analysis. Data were analyzed using SPSS for Windows statistical software (version 18.0; SPSS, Chicago, IL). Continuous variables were presented as mean ± SD with Pearson's correlation carried out where required. Discrete variables are presented in percentages with Spearman's correlation carried out where required. The χ² test (3 × 2 tables) was performed as defined at http://vassarstats.net/newcs.html Age-adjusted comparison of means was carried out. P < 0.05 was considered significant.

Results

Table 1 presents the general characteristics of the NGT subgroups stratified based on the 1hPG levels as <143 mg/dL, ≥143 to <155 mg/dL, and 1hPG ≥155 mg/dL. As the subgroups differed significantly in terms of age (P = 0.012), age-adjusted values are presented in Table 1. Serum cholesterol (P = 0.147), serum triglycerides (P = 0.048), and low-density lipoprotein cholesterol (P = 0.019) levels were higher in NGT subjects with elevated 1hPG values.

Table 1.

Anthropometric and Biochemical Profile (Age-Adjusted) of Normal Glucose Tolerance Subjects (n = 166) Stratified by the 1-H Plasma Glucose Cutoffs

	1hPG
Parameter	<143 mg/dL (n = 100)	≥143 to <155 mg/dL (n = 36)	≥155 mg/dL (n = 30)	P value
Age (years)	20 ± 5	22 ± 7	23 ± 6	0.012^a
Male (%)	46.1	66.7	46.7	0.094^b
Family history of diabetes (%)	81.0	83.3	76.9	0.817^b
BMI (kg/m²)	24.1 ± 6	25.7 ± 5.4	25.2 ± 5.5	0.301
Waist circumference (cm)	81.3 ± 13	83.7 ± 13.2	84.1 ± 13.1	0.477
Blood pressure (mm Hg)
Systolic	118 ± 17	121 ± 17	125 ± 16	0.168
Diastolic	74 ± 10	75 ± 10	77 ± 10	0.341
Serum cholesterol (mg/dL)	151 ± 29	156.5 ± 28.8	170.4 ± 28.5	0.005^a
Serum triglycerides (mg/dL)	91 ± 47	103 ± 47	113.9 ± 46.6	0.048^a
LDL cholesterol (mg/dL)	93 ± 24	99 ± 23	107 ± 24	0.019^a
Glycated hemoglobin (%)	5.4 ± 1	5.4 ± 0.6	5.6 ± 0.5	0.203
Plasma glucose (mg/dL)
Fasting (0 min)	79 ± 7	81 ± 6	80 ± 8	0.403
30 min	133 ± 19	150 ± 17	168 ± 23	<0.001
60 min	117 ± 15	147 ± 8	172 ± 14	<0.001
90 min	107 ± 16	123 ± 19	141 ± 19	<0.001
120 min	94 ± 18	103 ± 19	115 ± 15	<0.001
Plasma insulin (μIU/mL)
Fasting (0 min)	13 ± 8	16 ± 11	16 ± 8	0.15
30 min	124 ± 67	143 ± 74	166 ± 84	0.017^a
60 min	116 ± 64	184 ± 90	259 ± 142	<0.001
90 min	90 ± 59	127 ± 67	220 ± 121	<0.001
120 min	64 ± 45	87 ± 57	152 ± 93	<0.001

Data are age-adjusted mean ± SD values unless indicated otherwise.

Denotes statistically significant.

Spearman's correlation.

1hPG, 1-h plasma glucose; BMI, body mass index; LDL, low-density lipoprotein.

There were no significant differences in the fasting glucose and insulin levels among the groups. The curves began to separate by 30 min and differed significantly at all other time points during the OGTT (Table 1 and Supplementary Figure S1 [Supplementary Data are available online at www.liebertonline.com/dia]).

Table 2 presents the indices of β-cell function and insulin sensitivity.

Table 2.

Age-Adjusted Markers of β-Cell Function and Insulin Sensitivity Among Normal Glucose Tolerance Subjects (n = 166) Stratified by the 1-H Plasma Glucose Cutoffs

	1hPG
Parameter	<143 mg/dL (n = 100)	≥143 to <155 mg/dL (n = 36)	≥155 mg/dL (n = 30)	P value
Insulin secretion indices
HOMA-β (μIU_Ins, mmol_Glu) (0 min)	3.2 ± 2.1	3.7 ± 2.4	3.9 ± 1.9	0.236
Insulinogenic Index (pmol_Ins, mmol_Glu) (0 min)	367 ± 239	257 ± 243	246 ± 239	0.019^a
Insulin sensitivity indices
HOMA-IR (μIU_Ins, mmol_Glu) (0 min)	2.8 ± 2.0	3.4 ± 1.8	3.5 ± 1.6	0.103
Matsuda Index (pmol_Ins, mmol_Glu) (0–120 min)	11.2 ± 5.0	7.4 ± 4.8	5.5 ± 4.9	<0.001^a
Insulin Sensitivity Index (pmol_Ins) (0 min)	0.015 ± 0.010	0.012 ± 0.006	0.011 ± 0.011	0.028^a

Data are age-adjusted mean ± SD values.

Denotes statistically significant.

1hPG, 1-h plasma glucose; HOMA-β, homeostasis assessment model—β-cell function; HOMA-IR, homeostasis assessment model—insulin resistance; Glu, glucose; Ins, insulin.

Among the indices of β-cell function, the NGT subgroups did not differ significantly by HOMA-β. However, the IGI showed significantly lower β-cell function in the NGT subjects with elevated 1hPG values (P = 0.019).

With respect to the insulin sensitivity indices, the NGT groups did not differ significantly by HOMA-IR. However, the Matsuda Index (P < 0.001) and ISI (P = 0.028) showed significantly lower insulin sensitivity in the NGT subjects with elevated 1hPG values.

Discussion

Several groups^{4

–9,17
–19} have reported that NGT subjects with elevated 1hPG (i.e., those with values of ≥155 mg/dL during an OGTT) are more prone to develop T2DM in the future. In our earlier study on NGT subjects, we reported 1hPG predictive cutoffs of future prediabetes (1hPG of ≥143 to <155 mg/dL) and diabetes (1hPG of ≥155 mg/dL).⁴ In this article we report on various β-cell function insulin secretory and insulin sensitivity indices among NGT subjects stratified by the above 1hPG predictive cutoffs. To our knowledge, this is the first study of these indices among NGT in South Asians, an ethnic group known to have a highly susceptibility diabetogenic phenotype^20,21 and a rapid decline in β-cell function.^22,23

The key findings of the present study are that both β-cell function and insulin sensitivity are altered among subjects with elevated 1hPG values. These are not brought out well using fasting indices (e.g., HOMA-β or HOMA-IR), but they become evident if glucose-stimulated indices (i.e., IGI [representing β-cell function] and the Matsuda Index and ISI [representing insulin sensitivity]) are used.

We had earlier shown that in Asian Indians, both insulin secretory defects and insulin resistance are progressively worse in subjects with prediabetes and diabetes compared with NGT subjects.^22,23 In this report we show that similar defects can be seen even at the stage of NGT if subjects are stratified by the 1hPG levels. This suggests that insulin secretory and sensitivity defects (the major pathophysiological defects in T2DM) can be identified very early in the natural history of T2DM (i.e., even in the stage of NGT), at least in certain ethnic groups like Asian Indians.

One of the likely explanations why the fasting indices could not detect any significant differences between the NGT subgroups could be that fasting glucose and insulin values are more an indicator of hepatic, rather than peripheral, insulin resistance. One can hence speculate that hepatic insulin resistance is perhaps a later event and has not yet set in at the stage of NGT.^22,23 However, longitudinal studies using more sophisticated and precise techniques to measure β-cell function and insulin sensitivity are needed to establish this.

The present study is limited by its cross-sectional design, and hence cause-and-effect relationships cannot be drawn. Longitudinal studies are needed to investigate the changes in insulin secretory and sensitivity indices as one progresses from the NGT stage with normal 1-h levels through to elevated 1-h levels and then to the prediabetes and diabetes stages.

The small sample size is another limitation. As this is a clinic-based, “real world” population where offspring of parents with diabetes come to rule out diabetes, 80% of the study subjects had a family history of diabetes. This is one of the limitations of the study. However, the study variables did not differ from those with and without a family history of diabetes. Hence it is unlikely that this affected the results of the study.

Another limitation of the study is that we could not estimate insulin secretion and sensitivity using “gold standard measures” like hyperinsulinemic euglycemic clamp or the frequently sampled intravenous glucose tolerance test.^24,25 Such studies are urgently needed in this population. The strength of this study is that we have studied fasting and stimulated indices of β-cell function and insulin sensitivity in NGT subjects. Also to our knowledge, this is the first study in a relatively lean, non-white (south Asian) population.

A recent study in an East Asian (Korean) population compared NGT individuals with low (1hPG <155 mg/dL) and elevated (i.e., 1hPG ≥155 mg/dL) 1hPG levels with impaired glucose tolerance subjects; the study found that NGT subjects with 1hPG of >155 mg/dL exhibited similar β-cell function to impaired glucose tolerance individuals.⁶ An Italian study also showed similar findings.²⁶

Recent studies have shown that NGT subjects with elevated 1hPG values have chronic subclinical inflammation, renal dysfunction, and an increased risk of developing cardiovascular disease.^{7,8,25

–32} These studies highlight the growing importance of measuring the intermediary values (i.e., the 1-h value during an OGTT). This was indeed in vogue many years ago but was subsequently dropped because all current diagnostic criteria for diabetes and prediabetes only use FPG and 2hPG cut points.¹ Studying the 1hPG value during OGTT may help to detect earlier stages of the natural history of T2DM and thus help in planning effective strategies in the prevention of T2DM. Well-planned longitudinal studies could shed more light on the natural history of T2DM in different populations.

Footnotes

Author Disclosure Statement

No competing financial interests exist.

M.M.P. and V.M. conceived the study. V.M. and R.M.A. supervised the study and revised the manuscript. M.M.P. coordinated, performed the study, carried out the statistical analysis, and wrote the first draft of the article. A.A., H.R., K.G., R.U., R.P., T.A.P., and S.J. provided valuable inputs and helped revise the manuscript.

References

American Diabetes Association: Standards of medical care in diabetes—2015: summary of revisions. Diabetes Care, 2015; 38(Suppl 1):S4.

Unwin

, Shaw

, Zimmet

, Alberti

KGMM

: Impaired glucose tolerance and impaired fasting glycemia: the current status on definition and intervention. Diabet Med, 2002; 19:708–723.

Dagogo-Jack

, Edeoga

, Ebenibo

, Nyenwe

, Wan

; Pathobiology of Prediabetes in a Biracial Cohort (POP-ABC) Research Group: Lack of racial disparity in incident prediabetes and glycemic progression among black and white offspring of parents with type 2 diabetes: the pathobiology of prediabetes in a biracial cohort (POP-ABC) study. J Clin Endocrinol Metab, 2014; 99:E1078–E1087.

Priya

, Anjana

, Chiwanga

, Gokulakrishnan

, Deepa

, Mohan

: 1-hour venous plasma glucose and incident prediabetes and diabetes in Asian Indians. Diabetes Technol Ther, 2013; 15:497–502.

Strandberg

, Pienimaki

, Pitkala

, Tilvis

, Salomaa

, Strandberg

: Comparison of normal fasting and one-hour glucose levels as predictors of future diabetes during a 34-year follow-up. Ann Med, 2013; 45:336–340.

, Min

, Ahn

, Kim

, Kwak

, Jung

, Park

, Cho

: Normal glucose tolerance with a high 1-hour postload plasma glucose level exhibits decreased β-cell function similar to impaired glucose tolerance. Diabetes Metab J, 2015; 39:147–153.

Marini

, Succurro

, Frontoni

, Mastroianni

, Arturi

, Sciacqua

, Lauro

, Hribal

, Perticone

, Sesti

: Insulin sensitivity, beta-cell function, and incretin effect in individuals with elevated 1-hour postload plasma glucose levels. Diabetes Care, 2012; 35:868–872.

Winner

, Norton

, Kanat

, Arya

, Fourcaudot

, Hansis-Diarte

, Tripathy

, DeFronzo

, Jenkinson

, Abdul-Ghani

: Strong association between insulin-mediated glucose uptake and the 2-hour, not the fasting plasma glucose concentration, in the normal glucose tolerance range. J Clin Endocrinol Metab, 2014; 99:3444–3449.

Patarrão

, Lautt

, Macedo

: Assessment of methods and indexes of insulin sensitivity [in English, Portuguese]. Rev Port Endocrinol Diabetes Metab, 2014; 9:65–73.

10.

Friedewald

, Levy

, Fredrickson

: Estimation of the concentration of low-density lipoprotein cholesterol in plasma without use of the preparative ultracentrifuge. Clin Chem, 1972; 18:499–502.

11.

Matthews

, Hosker

, Rudenski

, Naylor

, Treacher

, Turner

: Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia, 1985; 28:412–419.

12.

DeFronzo

, Matsuda

: Reduced time points to calculate the composite index. Diabetes Care, 2010; 33:e93.

13.

, Zhu

, Jing

, Hu

, Feng

, Shen

, Tong

, Shen

, Yu

, Song

, Yang

: Decreased beta cell function and insulin sensitivity contributed to increasing fasting glucose in Chinese. Acta Diabetol, 2012; 49(Suppl 1):S51–S58.

14.

Wang

, Hu

, Feng

: Decreased beta cell function and insulin sensitivity contributed to coronary artery disease in patients with normal glucose tolerance. J Atheroscler Thromb, 2012; 19:806–813.

15.

Retnakaran

, Shen

, Hanley

, Vuksan

, Hamilton

, Zinman

: Hyperbolic relationship between insulin secretion and sensitivity on oral glucose tolerance test. Obesity (Silver Spring), 2008; 16:1901–1907.

16.

Matsuda

, DeFronzo

: Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care, 1999; 22:1462–1470.

17.

Alyass

, Almgren

, Akerlund

, Dushoff

, Isomaa

, Nilsson

, Tuomi

, Lyssenko

, Groop

, Meyre

: Modelling of OGTT curve identifies 1 h plasma glucose level as a strong predictor of incident type 2 diabetes: results from two prospective cohorts. Diabetologia, 2015; 58:87–97.

18.

Lind

, Tuomilehto

, Uusitupa

, Nerman

, Eriksson

, Ilanne-Parikka

, Keinänen-Kiukaanniemi

, Peltonen

, Pivodic

, Lindström

: The association between HbA1c, fasting glucose, 1-hour glucose and 2-hour glucose during an oral glucose tolerance test and cardiovascular disease in individuals with elevated risk for diabetes. PLoS One, 2014; 9:e109506.

19.

Sesti

, Fiorentino

, Succurro

, Perticone

, Arturi

, Sciacqua

, Perticone

: Elevated 1-h post-load plasma glucose levels in subjects with normal glucose tolerance are associated with unfavorable inflammatory profile. Acta Diabetol, 2014; 51:927–932.

20.

Gujral

, Pradeepa

, Weber

, Narayan

, Mohan

: Type 2 diabetes in South Asians: similarities and differences with white Caucasian and other populations. Ann N Y Acad Sci, 2013; 1281:51–63.

21.

Unnikrishnan

, Anjana

, Mohan

: Diabetes in South Asians: is the phenotype different?. Diabetes, 2014; 63:53–55.

22.

Mohan

, Amutha

, Ranjani

, Unnikrishnan

, Datta

, Anjana

, Staimez

, Ali

, Narayan

: Associations of β-cell function and insulin resistance with youth-onset type 2 diabetes and prediabetes among Asian Indians. Diabetes Technol Ther, 2013; 15:315–322.

23.

Staimez

, Weber

, Ranjani

, Ali

, Echouffo-Tcheugui

, Phillips

, Mohan

, Narayan

: Evidence of reduced β-cell function in Asian Indians with mild dysglycemia. Diabetes Care, 2013; 36:2772–2778.

24.

George

, Bacha

, Lee

, Tfayli

, Andreatta

, Arslanian

: Surrogate estimates of insulin sensitivity in obese youth along the spectrum of glucose tolerance from normal to prediabetes to diabetes. J Clin Endocrinol Metab, 2011; 96:2136–2145.

25.

Yeckel

, Weiss

, Dziura

, Taksali

, Dufour

, Burgert

, Tamborlane

, Caprio

: Validation of insulin sensitivity indices from oral glucose tolerance test parameters in obese children and adolescents. J Clin Endocrinol Metab, 2004; 89:1096–1101.

26.

Bianchi

, Miccoli

, Trombetta

, Giorgino

, Frontoni

, Faloia

, Marchesini

, Dolci

, Cavalot

, Cavallo

, Leonetti

, Bonadonna

, Del Prato

; GENFIEV Investigators: Elevated 1-hour postload plasma glucose levels identify subjects with normal glucose tolerance but impaired beta-cell function, insulin resistance, and worse cardiovascular risk profile: the GEN-FIEV study. J Clin Endocrinol Metab, 2013; 98:2100–2105.

27.

Shimodaira

, Niwa

, Nakajima

, Kobayashi

, Hanyu

, Nakayama

: Correlation between serum lipids and 1-hour post-load plasma glucose levels in normoglycemic individuals. J Clin Lipidol, 2014; 8:217–222.

28.

Sonmez

, Yilmaz

, Saglam

, Unal

, Gok

, Cetinkaya

, Karaman

, Haymana

, Eyileten

, Oguz

, Vural

, Rizzo

, Toth

: The role of plasma triglyceride/high density lipoprotein cholesterol ratio to predict cardiovascular outcomes in chronic kidney disease. Lipids Health Dis, 2015; 14:29.

29.

Sciacqua

, Maio

, Miceli

, Pascale

, Carullo

, Grillo

, Arturi

, Sesti

, Perticone

: Association between one-hour post-load plasma glucose levels and vascular stiffness in essential hypertension. PLoS One, 2012; 7:e44470.

30.

Niijima

, Muranaka

, Ando

, Okada

, Niijima

, Hashimoto

, Yamada

, Ohshima

, Mori

, Ono

: Elevated 1-h plasma glucose following 75-g oral glucose load is a predictor of arterial stiffness in subjects with normal glucose tolerance. Diabet Med, 2012; 29:e457–e460.

31.

Succurro

, Arturi

, Lugarà

, Grembiale

, Fiorentino

, Caruso

, Andreozzi

, Sciacqua

, Hribal

, Perticone

, Sesti

: One-hour postload plasma glucose levels are associated with kidney dysfunction. Clin J Am Soc Nephrol, 2010; 5:1922–1927.

32.

Kim

, Kim

, Park

, Oh

, Park

, Shin

, Lee

, Park

: Plasma glucose regulation and mortality in Korea: a pooled analysis of three community-based cohort studies. Diabetes Metab J, 2014; 38:44–50.

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