Exp Clin Endocrinol Diabetes 2014; 122(7): 384-386
DOI: 10.1055/s-0034-1366278
German Diabetes Associaton: Clinical Practice Guidelines
© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

Definition, Classification and Diagnosis of Diabetes Mellitus

W. Kerner
1  Klinik für Diabetes und Stoffwechselkrankheiten, Klinikum Karlsburg
,
J. Brückel
2  Abteilung Innere Medizin, Oberschwaben Klinik, Krankenhaus Wangen
› Author Affiliations
Further Information

Correspondence

Prof. Dr. med. Wolfgang Kerner
Klinikum Karlsburg Klinik für Diabetes und Stoffwechselkrankheiten
Greifswalder Str. 11
17495 Karlsburg
Phone: 03 83 55/70 13 97   
Fax: 03 83 55/70 15 82   

Publication History

Publication Date:
11 July 2014 (online)

 

Definition

Diabetes mellitus is a general term for heterogeneous disturbances of metabolism for which the main finding is chronic hyperglycaemia. The cause is either impaired insulin secretion or impaired insulin action or both.


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Classification

Type 1 Diabetes

  • β-cell destruction which leads to absolute insulin deficiency

  • Usually mediated by immune mechanisms

  • LADA (latent autoimmune diabetes in adults) is classified as type 1 diabetes.


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Type 2 Diabetes

  • Can range from predominant insulin resistance with relative insulin deficiency to prevailing defective secretion with insulin resistance.

  • Is frequently associated with other problems of the so-called metabolic syndrome


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Other Specific Diabetes Types

  • Diseases of the exocrine pancreas (e. g. pancreatitis, cystic fibrosis, hemochromatosis)

  • Endocrinopathies (e. g. Cushing syndrome, acromegaly, pheochromocytoma)

  • Drug induced (e. g. glucocorticoids, neuroleptics, alpha-interferons, pentamidine)

  • Genetic defects of the β-cell function (e. g. MODY forms)

  • Genetic defects of insulin action

  • Other genetic syndromes which can be associated with diabetes

  • Infections

  • Rare forms of auto-immune mediated diabetes


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Gestational Diabetes

Glucose tolerance impairments that first appear or are first diagnosed during pregnancy.


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Diagnostic Criteria

Important

Only standardised, quality assured laboratory methods may be applied when venous plasma glucose and HbA1c are measured. The current gold standard for diagnosing diabetes is measurement of glucose in venous plasma. This measurement can be accurate only if glycolysis is inhibited in the blood sample as soon as the sample is drawn. This can be done in two ways. Either the blood tube is stored on ice and the blood is centrifuged within 30 minutes, or glycolysis in the tube is effectively inhibited by appropriate additives (citrate plus fluoride; fluoride by itself is not sufficient). The glucose levels stated in the practice guidelines apply to venous plasma. (These levels correspond to the recommendations of the Deutsche Gesellschaft für Klinische Chemie und Laboratoriumsmedizin (DGKL) and the Deutsche Diabetes Gesellschaft (DDG)).


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Diabetes Mellitus

  • HbA1c ≥ 6.5 % (≥ 48 mmol/mol)

  • Random plasma glucose ≥ 200 mg/dl (≥ 11.1 mmol/l)

  • Fasting plasma glucose ≥ 126 mg/dl (≥ 7.0 mmol/dl)

  • OGTT 2‑hour glucose in venous plasma ≥ 200 mg/dl (≥ 11.1 mmol/l)

These guidelines have been recommending the use of HbA1c for diagnosing diabetes since 2010. This became possible through international standardisation of the measurement method. On the other hand, epidemiological investigations in recent years have shown that the specificity of HbA1c ≥ 6.5 % is high enough to justify a diagnosis of diabetes and the sensitivity of HbA1c < 5.7 % is high enough to justify exclusion of a diagnosis of diabetes. For these reasons, HbA1c is suitable as a primary diagnostic tool for excluding diabetes with great certainty and for making a diagnosis of diabetes in some cases. When the HbA1c level lies between 5.7 and 6.4 %, these guidelines recommend that diabetes and prediabetes be diagnosed by measuring glucose in accordance with traditional criteria. See [Fig. 1], [2] in the annex for the recommended diagnostic approach. The HbA1c level cannot be applied to making a diagnosis if an inaccurate HbA1c level is to be expected due to any of the factors stated in [Table 2].

See [Table 4] for details on OGTT and [Table 1] for differential diagnostic criteria for type 1 and type 2 diabetes.


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Impaired Fasting Glucose

IFG for fasting glucose levels from 100‑125 mg/dl (5.6 mmol-6.9 mmol/l) in venous plasma.


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Impaired Glucose Tolerance

IGT for 2‑hour plasma glucose in the OGIT in the range of 140‑199 mg/dl (7.8‑11.0 mmol/l) with fasting glucose < 126 mg/dl (< 7.0 mmol/l).


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Gestational Diabetes

The OGTT diagnostic criteria given in [Table 3] are based on the recently published results of the HAPO study. The differences to the previous borderline values are small, but but now gestational diabetes is indicated if any one (rather than at least two) of these values is exceeded.


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Annex


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Table 1 Differential Diagnostic Criteria for Type 1 and Type 2 Diabetes.

Type 1 Diabetes*

Type 2 Diabetes

Manifestation age

Mostly children, adolescents and young adults

Mostly middle and old age

Onset

Acute to subacute

Usually gradual

Symptoms

Frequently polyuria, polydipsia, weight loss, fatigue

Frequently no complaints

Body weight

Usually normal

Usually overweight

Predisposition to ketosis

Pronounced

None or only slight

Insulin secretion

Reduced or none

Below normal to high, qualitatively always impaired

Insulin resistance

None (or only low)

Often pronounced

Frequency in patient’s family history

Usually negative

Typically positive

Concordance with identical twins

30 to 50 %

Over 50 %

Heredity

Multifactorial (polygenetic)

Multifactorial (most likely polygenetic, but genetic heterogeneity is possible)

Associated with HLA (leukocyte antigen) system

Present

Not present

Antibodies associated with diabetes

Approx. 90‑95 % at onset (GAD, ICA, IA‑2, IAA)

None

Metabolism

Unstable

Stable

Response to insulin secretion stimulating antidiabetics

Usually none

Usually good at first

Insulin therapy

Required

Usually not required until insulin secretion has decreased after years of disease

* The LADA (latent autoimmune diabetes of adults) is associated with slower loss of beta cell function. Rapid failure of oral antidiabetics is to be expected. Analysis of GAD antibodies is recommended for cases of suspicion of LADA.

Table 2 Conditions which can lead to an inaccurate measurement of the HbA1c level.

1.

Haemoglobin variants (HbS, HbE, HbF, HbC, HbD and others)

the extent of the distortion depends on the method to determine HbA1c

2.

Conditions with increased or decreased lifetime of the erythrocytes (haemolytic anaemia, iron deficiency anaemia, blood formation in the context of anaemia treatment, liver disease, kidney disease)

3.

Chemical modifications of haemoglobin

uraemia (carbamylated Hb), high dosage long-time therapy with acetylsalicylic acid (acetylated Hb)

4.

Inhibition of glycation (e. g. long-time therapy with ascorbic acid or vitamin E)

the clinical significance of this phenomenon has not been studied well

5.

Pregnancy

Table 3 Diagnosis of Gestational Diabetes. Diabetes is present if one or more of the criteria in the table are fulfilled.

Venous plasma

mg/dl

mmol/l

Fasting

≥ 92

≥ 5.1

60 min.

≥ 180

≥ 10.0

120 min.

≥ 153

≥ 8.5

Table 4 Oral Glucose Tolerance Test (OGTT).

Procedure for the 75 g OGTT pursuant to WHO guidelines

Test must be performed in the morning

  • after 10 – 16 hours abstention from nutrients (and alcohol)

  • after at least 3 days of a diet rich in carbohydrates (≥ 150 g carbohydrates per day)

  • while sitting or lying down (no muscular effort), no smoking before or during the test

At time 0 drink 75 g glucose (or equivalent quantity of hydrolysed starch) dissolved in 250 – 300 ml water within 5 minutes.

  • children 1.75 g/kg body weight (at most 75 g)

  • take blood samples at times 0 and 120 minutes.

  • store and process the samples properly.

Test is contraindicated in case of a previous diagnosis of diabetes mellitus, gastric or intestinal resection, any gastrointestinal disease with changed resorption, or any intercurrent disease.

Zoom Image
Fig. 1 Diagnostic Flowchart (glucose mg/dl).
Zoom Image
Fig. 2 Diagnostic Flowchart (glucose mmol/l).

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Correspondence

Prof. Dr. med. Wolfgang Kerner
Klinikum Karlsburg Klinik für Diabetes und Stoffwechselkrankheiten
Greifswalder Str. 11
17495 Karlsburg
Phone: 03 83 55/70 13 97   
Fax: 03 83 55/70 15 82   


Zoom Image
Fig. 1 Diagnostic Flowchart (glucose mg/dl).
Zoom Image
Fig. 2 Diagnostic Flowchart (glucose mmol/l).