Advertisement
Clinical Science| Volume 63, ISSUE 12, P1553-1561, December 2014

Download started.

Ok

Increased glycemic variability and decrease of the postprandial glucose contribution to HbA1c in obese subjects across the glycemic continuum from normal glycemia to first time diagnosed diabetes

  • Marinos Fysekidis
    Affiliations
    AP-HP, Jean Verdier Hospital, Paris 13 University, Sorbonne Paris Cité, Department of Endocrinology–Diabetology–Nutrition, CRNH-IdF, CINFO, Bondy, France

    Sorbonne Paris Cité, UMR U1153 Inserm/U1125 Inra/Cnam/Université Paris 13, Bobigny, France
    Search for articles by this author
  • Emmanuel Cosson
    Affiliations
    AP-HP, Jean Verdier Hospital, Paris 13 University, Sorbonne Paris Cité, Department of Endocrinology–Diabetology–Nutrition, CRNH-IdF, CINFO, Bondy, France

    Sorbonne Paris Cité, UMR U1153 Inserm/U1125 Inra/Cnam/Université Paris 13, Bobigny, France
    Search for articles by this author
  • Isabela Banu
    Affiliations
    AP-HP, Jean Verdier Hospital, Paris 13 University, Sorbonne Paris Cité, Department of Endocrinology–Diabetology–Nutrition, CRNH-IdF, CINFO, Bondy, France
    Search for articles by this author
  • Régine Duteil
    Affiliations
    AP-HP, Jean Verdier Hospital, Paris 13 University, Sorbonne Paris Cité, Department of Endocrinology–Diabetology–Nutrition, CRNH-IdF, CINFO, Bondy, France
    Search for articles by this author
  • Chantal Cyrille
    Affiliations
    AP-HP, Jean Verdier Hospital, Paris 13 University, Sorbonne Paris Cité, Department of Endocrinology–Diabetology–Nutrition, CRNH-IdF, CINFO, Bondy, France
    Search for articles by this author
  • Paul Valensi
    Correspondence
    Corresponding author at: Department of Endocrinology–Diabetology–Nutrition, Jean Verdier Hospital, Avenue du 14 Juillet, 93143 Bondy Cedex, France. Tel.: +33 148026580; fax: +33 148026356.
    Affiliations
    AP-HP, Jean Verdier Hospital, Paris 13 University, Sorbonne Paris Cité, Department of Endocrinology–Diabetology–Nutrition, CRNH-IdF, CINFO, Bondy, France
    Search for articles by this author
Published:September 26, 2014DOI:https://doi.org/10.1016/j.metabol.2014.09.006

      Abstract

      Objective

      The contribution of postprandial glycemia (PPG) to hyperglycemia has been shown to decrease as HbA1c increased in type 2 diabetic patients. This study aimed at examining, in a series of overweight/obese patients without known glycemic disorder, the contribution of PPG to a “relative” hyperglycemia (glucose values ≥5.5 mmol/L) and the presence of glycemic variability according to HbA1c levels.

      Methods

      Seventy overweight/obese inpatients (body mass index 35.2 ± 6.8 kg/m2) without known glycemic disorder were included. Participants were classified according to an oral glucose tolerance test (according to the American Diabetes Association criteria) as patients with normoglycemia (n = 33), with intermediate hyperglycemia (n = 24) or diabetes (n = 13). They were separated into HbA1c quartiles (Q1 to Q4). A 24 hour continuous glucose monitoring was used under a 1800 kcal diet and minimal physical activity. We assessed PPG contribution (3 hour period after each meal) to the “relative” 24 hour hyperglycemia (glucose values ≥5.5 mmol/L); the remaining time was considered as the fasting/post-absorptive period.

      Results

      HbA1c range was from 5.1% to 7.4% (32 to 57 mmol/mmol). From the lowest to the highest HbA1c quartile, the area under the curve (AUC) for the “relative” hyperglycemia presented a 17-fold increase for the fasting/post-absorptive (p < 0.001) period and a 7-fold increase postprandially (p < 0.001). The percent of PPG contribution to the “relative” hyperglycemia was calculated with the following formula [100 × (postprandial 3 hour AUC − 3 h AUC for a constant 5.5 mmol/L glycemia)/(total 24 h AUC − 24 h AUC for constant 5.5 mmol/L glycemia)] and decreased from Q1 to Q4 of HbA1c (81.2%, 66%, 65.8%, 57%; p < 0.001). Increasing HbA1c quartiles were associated with higher daily mean blood glucose level (p < 0.001) and higher levels of daily glucose variability indices, including mean amplitude of glycemic excursions (p < 0.01).

      Conclusions

      In overweight/obese patients, HbA1c was associated with lower PPG contribution to “relative” hyperglycemia and greater glycemic variability. The present findings support the importance of postprandial period in glycemic exposure even before the appearance of diabetes.

      Abbreviations:

      HbA1c (Glycated Hemoglobin), CGM (Continuous Glucose Monitoring), PPG (Postprandial Glycemia), OGTT (Oral Glucose Tolerance Test), GV (Glycemic Variability), BMI (Body Mass Index), AUC (Area under the Curve), MBG (Mean Blood Glucose), MAGE (Mean Amplitude of Glycemic Excursions), SD (Daily Standard Deviation), CV% (Coefficient of Variation), CONGA (Continuous Overlapping Net Glycemic Action), HBGI (High Blood Glucose index), LBGI (Low Blood Glucose Index), LI (Lability Index), MAG (Mean Absolute Glucose), HOMA (Homeostasis Model Assessment)

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Metabolism - Clinical and Experimental
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

      1. International Expert Committee report on the role of the A1C assay in the diagnosis of diabetes.
        Diabetes Care. 2009; 32: 1327-1334
        • Stratton I.M.
        • Adler A.I.
        • Neil H.A.
        • et al.
        Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study.
        BMJ. 2000; 321: 405-412
        • Little R.R.
        • Rohlfing C.L.
        • Wiedmeyer H.M.
        • et al.
        The national glycohemoglobin standardization program: a five-year progress report.
        Clin Chem. 2001; 47: 1985-1992
        • Ollerton R.L.
        • Playle R.
        • Ahmed K.
        • et al.
        Day-to-day variability of fasting plasma glucose in newly diagnosed type 2 diabetic subjects.
        Diabetes Care. 1999; 22: 394-398
      2. Standards of medical care in diabetes — 2013.
        Diabetes Care. 2013; 36: S11-S66
        • Monnier L.
        • Lapinski H.
        • Colette C.
        Contributions of fasting and postprandial plasma glucose increments to the overall diurnal hyperglycemia of type 2 diabetic patients: variations with increasing levels of HbA(1c).
        Diabetes Care. 2003; 26: 881-885
        • Monnier L.
        • Colette C.
        • Owens D.R.
        Glycemic variability: the third component of the dysglycemia in diabetes. Is it important? How to measure it?.
        J Diabetes Sci Technol. 2008; 2: 1094-1100
      3. Glucose tolerance and mortality: comparison of WHO and American Diabetes Association diagnostic criteria. The DECODE study group. European Diabetes Epidemiology Group. Diabetes Epidemiology: Collaborative analysis Of Diagnostic criteria in Europe.
        Lancet. 1999; 354: 617-621
        • Brownlee M.
        • Hirsch I.B.
        Glycemic variability: a hemoglobin A1c-independent risk factor for diabetic complications.
        JAMA. 2006; 295: 1707-1708
        • Hirsch I.B.
        • Brownlee M.
        Should minimal blood glucose variability become the gold standard of glycemic control?.
        J Diabetes Complications. 2005; 19: 178-181
        • Monnier L.
        • Mas E.
        • Ginet C.
        • Michel F.
        • et al.
        Activation of oxidative stress by acute glucose fluctuations compared with sustained chronic hyperglycemia in patients with type 2 diabetes.
        JAMA. 2006; 295: 1681-1687
        • Ceriello A.
        • Novials A.
        • Ortega E.
        • et al.
        Evidence that hyperglycemia after recovery from hypoglycemia worsens endothelial function and increases oxidative stress and inflammation in healthy control subjects and subjects with type 1 diabetes.
        Diabetes. 2012; 61: 2993-2997
      4. U.K. Prospective Diabetes Study 16. Overview of 6 years’ therapy of type II diabetes: a progressive disease. U.K. Prospective Diabetes Study Group.
        Diabetes. 1995; 44: 1249-1258
        • Monnier L.
        • Colette C.
        • Dunseath G.J.
        • Owens D.R.
        The loss of postprandial glycemic control precedes stepwise deterioration of fasting with worsening diabetes.
        Diabetes Care. 2007; 30: 263-269
        • Pratley R.E.
        • Weyer C.
        The role of impaired early insulin secretion in the pathogenesis of type II diabetes mellitus.
        Diabetologia. 2001; 44: 929-945
        • Kanat M.
        • Norton L.
        • Winnier D.
        • et al.
        Impaired early- but not late-phase insulin secretion in subjects with impaired fasting glucose.
        Acta Diabetol. 2011; 48: 209-217
        • Reaven G.M.
        • Brand R.J.
        • Chen Y.D.
        • et al.
        Insulin resistance and insulin secretion are determinants of oral glucose tolerance in normal individuals.
        Diabetes. 1993; 42: 1324-1332
        • Paulweber B.
        • Valensi P.
        • Lindstrom J.
        • et al.
        A European evidence-based guideline for the prevention of type 2 diabetes.
        Horm Metab Res. 2010; 42: S3-S36
      5. Diagnosis and classification of diabetes mellitus.
        Diabetes Care. 2011; 34: S62-S69
        • Valensi P.
        • Lormeau B.
        • Dabbech M.
        • et al.
        Glucose-induced thermogenesis, inhibition of lipid oxidation rate and autonomic dysfunction in non-diabetic obese women.
        Int J Obes Relat Metab Disord. 1998; 22: 494-499
        • Monnier L.
        • Colette C.
        • Lapinski H.
        • Boniface H.
        Self-monitoring of blood glucose in diabetic patients: from the least common denominator to the greatest common multiple.
        Diabetes Metab. 2004; 30: 113-119
        • Hill N.R.
        • Oliver N.S.
        • Choudhary P.
        • Levy J.C.
        • et al.
        Normal reference range for mean tissue glucose and glycemic variability derived from continuous glucose monitoring for subjects without diabetes in different ethnic groups.
        Diabetes Technol Ther. 2011; 13: 921-928
        • Rodbard D.
        Interpretation of continuous glucose monitoring data: glycemic variability and quality of glycemic control.
        Diabetes Technol Ther. 2009; 11: S55-S67
        • Matthews D.R.
        • Hosker J.P.
        • Rudenski A.S.
        • et al.
        Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man.
        Diabetologia. 1985; 28: 412-419
        • DeFronzo R.A.
        • Matsuda M.
        Reduced time points to calculate the composite index.
        Diabetes Care. 2010; 33: e93
        • Cosson E.
        • Chiheb S.
        • Hamo-Tchatchouang E.
        • et al.
        Use of clinical scores to detect dysglycaemia in overweight or obese women.
        Diabetes Metab. 2012; 38: 217-224
        • Cosson E.
        • Nguyen M.T.
        • Hamo-Tchatchouang E.
        • et al.
        What would be the outcome if the American Diabetes Association recommendations of 2010 had been followed in our practice in 1998–2006.
        Diabet Med. 2011; 28: 567-574
        • An P.
        • Miljkovic I.
        • Thyagarajan B.
        • Kraja A.T.
        • et al.
        Genome-wide association study identifies common loci influencing circulating glycated hemoglobin (HbA1c) levels in non-diabetic subjects: the Long Life Family Study (LLFS).
        Metabolism. 2014; 63: 461-468
        • Ebenibo S.
        • Edeoga C.
        • Wan J.
        • Dagogo-Jack S.
        Glucoregulatory function among African Americans and European Americans with normal or pre-diabetic hemoglobin A1c levels.
        Metabolism. 2014; 63: 767-772
        • Nathan D.M.
        • Kuenen J.
        • Fau - Borg R.
        • et al.
        Translating the A1C assay into estimated average glucose values.
        Diabetes Care. 2008; 31: 1473-1478
        • Bock G.
        • Dalla Man C.
        • Campioni M.
        • et al.
        Pathogenesis of pre-diabetes: mechanisms of fasting and postprandial hyperglycemia in people with impaired fasting glucose and/or impaired glucose tolerance.
        Diabetes. 2006; 55: 3536-3549
        • Donahue R.P.
        • Abbott R.D.
        • Reed D.M.
        • Yano K.
        Postchallenge glucose concentration and coronary heart disease in men of Japanese ancestry. Honolulu Heart Program.
        Diabetes. 1987; 36: 689-692
        • de Vegt F.
        • Dekker J.M.
        • Ruhe H.G.
        • et al.
        Hyperglycaemia is associated with all-cause and cardiovascular mortality in the Hoorn population: the Hoorn Study.
        Diabetologia. 1999; 42: 926-931
        • Balkau B.
        • Shipley M.
        • Jarrett R.J.
        • et al.
        High blood glucose concentration is a risk factor for mortality in middle-aged nondiabetic men. 20-year follow-up in the Whitehall Study, the Paris Prospective Study, and the Helsinki Policemen Study.
        Diabetes Care. 1998; 21: 360-367
        • Meigs J.B.
        • Nathan D.M.
        • D'Agostino Sr., R.B.
        • Wilson P.W.
        Fasting and postchallenge glycemia and cardiovascular disease risk: the Framingham Offspring Study.
        Diabetes Care. 2002; 25: 1845-1850
        • Chiasson J.L.
        • Josse R.G.
        • Gomis R.
        • et al.
        Acarbose for the prevention of type 2 diabetes, hypertension and cardiovascular disease in subjects with impaired glucose tolerance: facts and interpretations concerning the critical analysis of the STOP-NIDDM Trial data.
        Diabetologia. 2004; 47: 969-975
        • Ma C.M.
        • Yin F.Z.
        • Wang R.
        • Qin C.M.
        • et al.
        Glycemic variability in abdominally obese men with normal glucose tolerance as assessed by continuous glucose monitoring system.
        Obesity (Silver Spring). 2011; 19: 1616-1622
        • Kramer C.K.
        • Fau Choi H.
        • Zinman B.
        • et al.
        Glycemic variability in patients with early type 2 diabetes: the impact of improvement in beta-cell function.
        Diabetes Care. 2014; 37: 1116-1123
        • Ceriello A.
        • Taboga C.
        • Tonutti L.
        • et al.
        Evidence for an independent and cumulative effect of postprandial hypertriglyceridemia and hyperglycemia on endothelial dysfunction and oxidative stress generation: effects of short- and long-term simvastatin treatment.
        Circulation. 2002; 106: 1211-1218
        • Selvin E.
        • Steffes M.W.
        • Zhu H.
        • et al.
        Glycated hemoglobin, diabetes, and cardiovascular risk in nondiabetic adults.
        N Engl J Med. 2010; 362: 800-811
        • Papanas N.
        • Ziegler D.
        Polyneuropathy in impaired glucose tolerance: is postprandial hyperglycemia the main culprit? A mini-review.
        Gerontology. 2013; 59: 193-198
        • Singleton J.R.
        • Smith A.G.
        • Russell J.W.
        • Feldman E.L.
        Microvascular complications of impaired glucose tolerance.
        Diabetes. 2003; 52: 2867-2873
        • Kilpatrick E.S.
        • Rigby A.S.
        • Atkin S.L.
        The effect of glucose variability on the risk of microvascular complications in type 1 diabetes.
        Diabetes Care. 2006; 29: 1486-1490
        • Siegelaar S.E.
        • Kerr L.
        • Jacober S.J.
        • Devries J.H.
        A decrease in glucose variability does not reduce cardiovascular event rates in type 2 diabetic patients after acute myocardial infarction: a reanalysis of the HEART2D study.
        Diabetes Care. 2011; 34: 855-857
        • Baghurst P.A.
        • Rodbard D.
        • Cameron F.J.
        The minimum frequency of glucose measurements from which glycemic variation can be consistently assessed.
        J Diabetes Sci Technol. 2010; 4: 1382-1385