Impact of fasting and postprandial glycemia on overall glycemic control in type 2 diabetes: Importance of postprandial glycemia to achieve target HbA1c levels

doi:10.1016/j.diabres.2006.11.011

Diabetes Research and Clinical Practice

Volume 77, Issue 2, August 2007, Pages 280-285

https://doi.org/10.1016/j.diabres.2006.11.011 Get rights and content

Abstract

Objective

HbA1c values reflect overall glycemic exposure over the past 2–3 months and are determined by both fasting (FPG) and postprandial plasma glucose (PPG) levels. Cross-sectional studies suggest that attainment of HbA1c goals requires specific targeting of postprandial hyperglycemia.

Research design and methods

We undertook a prospective intervention trial to assess the relative contribution of controlling FPG and PPG for achieving recommended HbA1c goals. One hundred and sixty-four patients (90 male and 74 female) with unsatisfactory glycemic control (HbA1c ≥7.5%) were enrolled in an individualized forced titration intensified treatment program.

Results

After 3 months HbA1c levels decreased from 8.7 ± 0.1 to 6.5 ± 0.1% (p < 0.001); FPG decreased from 174 ± 4 to 117 ± 2 mg/dl (p < 0.001); PPG decreased from 224 ± 4 to 159 ± 3 mg/dl (p < 0.001) and daylong hyperglycemia (average of premeal, postprandial and bedtime plasma glucose excluding FPG) decreased from 199 ± 4 to 141 ± 2 mg/dl (p < 0.0001). Patients’ weight remained unchanged (84.0 ± 1.4 kg versus 82.9 ± 1.5 kg, p = 0.36). No severe hypoglycemia occurred. Only 64% of patients achieving FPG targets of <100 mg/dl achieved an HbA1c target of <7% whereas 94% of patients achieving the postprandial target of <140 mg/dl did. Decreases in PPG accounted for nearly twice as much for the decreases in HbA1c as did decreases in FPG. PPG accounted ∼80% of HbA1c when HbA1c was <6.2% and only about 40% when HbA1c was above 9.0%.

Conclusions

Control of fasting hyperglycemia is necessary but usually insufficient for achieving HbA1c goals <7%. Control of postprandial hyperglycemia is essential for achieving recommended HbA1c goals.

Introduction

Controlled clinical trials have demonstrated that reducing HbA1c lessens the risk of micro- and macrovascular complications for patients with type 2 diabetes [1], [2], [3], [4]. The American Diabetes Association currently recommends HbA1c levels of ≤7.0% [5]. The International Diabetes Federation [6] and American Association of Clinical Endocrinologists [7] recommend a target of ≤6.5% based on evidence that more strict glycemic control might be necessary to prevent macrovascular complications [1], [8], [9].

HbA1c levels reflect overall glycemic exposure over the past 2–3 months and are determined by both fasting and postprandial plasma glucose (PPG) exposure. Cross-sectional studies suggest that attainment of recommended HbA1c goals of <7.0 or 6.5% may require specific targeting of postprandial hyperglycemia [10], [11].

We therefore undertook a prospective study to assess the relative contribution of controlling fasting and postprandial hyperglycemia in achieving recommended HbA1c goals. One hundred and sixty-four patients with type 2 diabetes having HbA1c levels >7.5% were treated for 3 months with individualized forced titration regimens designed to reduce their FPG to ≤100 mg/dl and their 90 min postmeal plasma glucose to ≤140 mg/dl. Our results indicate that targeting postprandial hyperglycemia is essential to optimise glycemic control and that this can be achieved without either unacceptable weight gain or increased risk for severe hypoglycemia.

Section snippets

Methods

One hundred and sixty-four subjects (90 male and 74 female) with suboptimal glycemic control (HbA1c levels >7.5%) were enrolled in the study after giving informed consent. Demographic characteristics and treatment regimens before and after 3 months are given in Table 1.

At the first clinic visit venous blood samples were obtained for determination of HbA1c levels. Subjects were trained to use a self monitoring blood glucose device (Ascensia elite, Dex 2, Bayer, Accu-Chek Comfort, Free Style,

Overview of approach

The initial goal of therapy intensification was aimed at achieving an FPG of <100 mg/dl. If initial FPG was >100 but <140 mg/dl on diet alone, metformin was given. If on a sulfonylurea metformin was added. If FPG <100 mg/dl was not achieved on metformin with or without a sulfonylurea NPH insulin at bedtime was initiated and titrated based on FPG levels and the sulfonylurea was discontinued. NPH-insulin was injected in the thigh since this prolongs the duration of the insulin. In case of fasting

Statistical analyses

Data are given as means ± S.E.M. unless otherwise specified and were analysed using Statistica (98 edition, Statsoft, Inc., Tulsa, OK). Comparisons were performed using the Chi-squared test and either paired or non-paired two tailed Student's t-tests.

Results over sixtiles were evaluated by ANOVA followed by post hoc comparison. A p ≤ 0.05% was considered to be statistically significant.

Results

Table 1 gives baseline characteristics of subjects and their treatment regimens. Prior to initiation of the intensified treatment program, 26% of patients were being managed by diet alone whereas on the intensified treatment program this decreased to 4%. The proportion of subjects treated with oral hypoglycemic agents alone decreased from 44 to 26% whereas the number of subjects treated with insulin alone or in combination with oral hypoglycemic agents increased from 31 to 70%.

The effects of

Discussion

The present study was undertaken to determine the relative importance of improvements in fasting and postprandial hyperglycemia for achievement of optimal glycemic control in patients with type 2 diabetes. We enrolled 164 patients with type 2 diabetes having an initial HbA1c >7.5% (mean ∼8.7%) in an intensified forced titration program aimed to achieve FPG levels ≤100 mg/dl and postprandial plasma glucose levels ≤140 mg/dl. Three months of this intensified therapy resulted in significant

Acknowledgments

We thank Mary Little for her excellent editorial assistance. The present work was supported in part by the National Institute of Diabetes and Digestive and Kidney Diseases Grant DK-20411 to John Gerich and a General Clinical Research Center Grant, 5MO1 RR-00044, from the National Center for Research Resources, NIH and the Deutsche Forschungsgemeinschaft Grant to Hans J. Woerle and Joerg Schirra.

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Impact of fasting and postprandial glycemia on overall glycemic control in type 2 diabetes: Importance of postprandial glycemia to achieve target HbA1c levels

Abstract

Objective

Research design and methods

Results

Conclusions

Introduction

Section snippets

Methods

Overview of approach

Statistical analyses

Results

Discussion

Acknowledgments

Diabetes Res. Clin. Pract.

Endocr. Pract.

Am. J. Obstet. Gynecol.

Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33)

Lancet

Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34)

Lancet

Long-term results of the Kumamoto Study on optimal diabetes control in type 2 diabetic patients

Diabetes Care