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Journal of Diabetes and Metabolism DOI: 10.4172/2155-6156.1000541
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ISSN: 2155-6156

Review Article Open Access

Classification, Pathophysiology, Diagnosis and Management of Diabetes

Mellitus
Habtamu Wondifraw Baynest
University of Gondar, Ethopia

Abstract
Diabetes Mellitus (DM) is a metabolic disorder characterized by the presence of chronic hyperglycemia either
immune-mediated (Type 1 diabetes), insulin resistance (Type 2), gestational or others (environment, genetic
defects, infections, and certain drugs). According to International Diabetes Federation Report of 2011 an estimated
366 million people had DM, by 2030 this number is estimated to almost around 552 million. There are different
approaches to diagnose diabetes among individuals, The 1997 ADA recommendations for diagnosis of DM focus on
fasting Plasma Glucose (FPG), while WHO focuses on Oral Glucose Tolerance Test (OGTT). This is importance for
regular follow-up of diabetic patients with the health care provider is of great significance in averting any long term
complications.

Keywords: Diabetes mellitus; Epidemiology; Diagnosis; Glycemic Unfortunately, the improvement in outcomes for individual patients
management with diabetes has not resulted in similar improvements from the public
health perspective.
Abbreviations: DM: Diabetes Mellitus; FPG: Fasting Plasma
Glucose; GAD: Glutamic Acid Decarboxylase; GDM: Gestational The worldwide prevalence of diabetes has continued to increase
Diabetes Mellitus; HDL-cholesterol: High Density Lipoprotein dramatically. Globally, as of 2011, an estimated 366 million people had
cholesterol; HLA: Human Leucoid Antigen; IDDM: Insulin Dependent DM, with type 2 making up about 90% of the cases [9,10]. The number
Diabetes Mellitus; IFG: Impaired Fasting Glucose; IGH: Increased of people with type 2 DM is increasing in every country with 80% of
Glycated Hemoglobin; IGT: Impaired Glucose Test; NIDDM: Non- people with DM living in low- and middle-income countries. Literature
Insulin Dependent Diabetes Mellitus; OGTT: Oral Glucose Tolerance search has shown that there are few data available on the prevalence of
Test type 2 DM in Africa as a whole. Studies examining data trends within
Africa point to evidence of adramatic increase in prevalence in both
Introduction rural and urban setting, and affecting both gender proportionally
Diabetes Mellitus (DM) is a metabolic disorder characterized by the [11]. According to the World Fact book report in 2008, in Africa the
presence of chronic hyperglycemia accompanied by greater or lesser prevalence of diabetes mellitus was 3.2%, and 40,895 persons (2.0%)
impairment in the metabolism of carbohydrates, lipids and proteins. was in Ethiopia [12].
DM is probably one of the oldest diseases known to man. It was first Although T2DM is widely diagnosed in adults, its frequency
reported in Egyptian manuscript about 3000 years ago [1]. In 1936, the has markedly increased in the pediatric age group over the past two
distinction between type 1 and type 2 DM was clearly made [2]. Type decades. Depending on the population studied, T2DM now represents
2 DM was first described as a component of metabolic syndrome in 8-45% of all new cases of diabetes reported among children and escent
1988 [3]. [13]. The prevalence of T2DM in the pediatric population is higher
The origin and etiology of DM can vary greatly but always include among girls than boys, just as it is higher among women than men [14].
defects in either insulin secretion or response or in both at some point The mean age of onset of T2DM is 12-16 years; this period coincides
in the course of disease. Mostly patients with diabetes mellitus have with puberty, when a physiologic state of insulin resistance develops.
either type 1 diabetes (which is immune-mediated or idiopathic) In this physiologic state, T2DM develops only if inadequate beta-cell
Type 2 DM (formerly known as non-insulin dependent DM) is the function is associated with other risk factors (e.g. obesity) [15].
most common form of DM characterized by hyperglycemia, insulin
resistance, and relative insulin deficiency [4]. Certain literatures also stated that T1DM is the most common form
of diabetes in most part of the world. Wide variations exist between the
Type 2 DM results from interaction between genetic, environmental
and behavioral risk factors [5,6]. Diabetes also can be related to the
gestational hormonal environment, genetic defects, other infections,
and certain drugs [7]. *Corresponding author: Habtamu Wondifraw Baynes, Lecturer Clinical Chemistry,
University of Gondar, Gondar, Amhara 196, Ethiopia, Tel: +251910818289; E-mail:
Epidemiology [email protected]

Received March 16, 2015; Accepted April 27, 2015; Published April 30, 2015
The application of epidemiology to the study of DM has provided
valuable information on several aspects of this disease such as its Citation: Baynes HW (2015) Classification, Pathophysiology, Diagnosis and
Management of Diabetes Mellitus. J Diabetes Metab 6: 541. doi:10.4172/2155-
natural history, prevalence, incidence, morbidity and mortality in 6156.1000541
diverse populations around the world. Identification of the cause of the
disease and the possible preventive measures that could be instituted Copyright: © 2015 Baynes HW. This is an open-access article distributed under
the terms of the Creative Commons Attribution License, which permits unrestricted
to arrest or delay the onset of this disease which has reached epidemic use, distribution, and reproduction in any medium, provided the original author and
proportions in both the developed and the developing nations [8]. source are credited.

J Diabetes Metab Volume 6 • Issue 5 • 1000541

ISSN: 2155-6156 JDM, an open access journal
Citation: Baynes HW (2015) Classification, Pathophysiology, Diagnosis and Management of Diabetes Mellitus. J Diabetes Metab 6: 541.
doi:10.4172/2155-6156.1000541

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incidence rates of different populations, incidence is lowest in China exhibit intra-abdominal (visceral) obesity, which is closely related
(0.1 per 105 per year) and highest in Finland (37 per 105 per year).In to the presence of insulin resistance. In addition, hypertension and
most populations girls and boys are equally affected. In general, the dyslipidemia (high triglyceride and low HDL-cholesterol levels;
incidence increases with age, the incidence peak is at puberty. After the postprandial hyperlipidemia) often are present in these individuals.
pubertal years, the incidence rate significantly drops in young women, This is the most common form of diabetes mellitus and is highly
but remains relatively high in young adult males up to the age 29-35 associated with a family history of diabetes, older age, obesity and lack
years [16]. of exercise. It is more common in women, especially women with a
history of gestational diabetes, and in Blacks, Hispanics and Native
Presently as many as 50% of people with diabetes are undiagnosed. Americans.
Since therapeutic intervention can reduce complications of the
disease, there is a need to detect diabetes early in its course. The risk Gestational Diabetes Mellitus (GDM)
of developing Type 2 diabetes increases with age, obesity, and lack of
Gestational diabetes mellitus is an operational classification
physical activity. Its incidence is increasing rapidly, and by 2030 this
(rather than a pathophysiologic condition) identifying women who
number is estimated to almost around 552 million [17,5].  Diabetes develop diabetes mellitus during gestation. Women who develop Type
mellitus occurs throughout the world, but is more common (especially 1 diabetes mellitus during pregnancy and women with undiagnosed
type 2) in the more developed countries, where the majority of patients asymptomatic Type 2 diabetes mellitus that is discovered during
are aged between 45 and 64 years. The greatest increase in prevalence pregnancy are classified with Gestational Diabetes Mellitus (GDM). In
is, however, expected to occur in Asia and Africa, where most patients most women who develop GDM; the disorder has its onset in the third
will probably be found by 2030 [5] (Table 1).  It is projected that the trimester of pregnancy.
latter will equal or even exceed the former in developing nations, thus
culminating in a double burden as a result of the current trend of Other specific type (Monogenic diabetes)
transition from communicable to non-communicable diseases [18].
Types of diabetes mellitus of various known etiologies are grouped
Classification of Diabetes Mellitus together to form the classification called “Other Specific Types”. This
group includes persons with genetic defects of beta-cell function (this
If any characteristic can define the new intentions for DM type of diabetes was formerly called MODY or maturity-onset diabetes
classification, it is the intention to consolidate etiological views in youth) or with defects of insulin action; persons with diseases of the
concerning DM. The old and confusing terms of insulin-dependent exocrine pancreas, such as pancreatitis or cystic fibrosis; persons with
(IDDM) or non-insulin-dependent (NIDDM) which were proposed dysfunction associated with other endocrinopathies (e.g. acromegaly);
by WHO in1980 and 1985 have disappeared and the terms of new and persons with pancreatic dysfunction caused by drugs, chemicals or
classification system identifies four types of diabetes mellitus: type 1, infections and they comprise less than 10% of DM cases.
type 2, “other specific types” and gestational diabetes [6]. The etiologic
classifications of diabetes mellitus are listed in (Table 2). Clinical Features of Diabetes Mellitus
Type 1 diabetes mellitus General symptoms
Type 1 diabetes mellitus (juvenile diabetes) is characterized by beta Most of the symptoms are similar in both types of diabetes but
cell destruction caused by an autoimmune process, usually leading they vary in their degree and develop more rapidly in type 1 diabetes
to absolute insulin deficiency [20]. Type 1 is usually characterized by and more typical.
the presence of anti–glutamic acid decarboxylase, islet cell or insulin
antibodies which identify the autoimmune processes that lead to beta
Clinical features of type I diabetes
cell destruction. Eventually, all type1 diabetic patients will require Some of the symptoms include weight loss, polyurea, polydipsia,
insulin therapy to maintain normglycemia. polyphagia, constipation fatigue, cramps, blurred vision, and
candidiasis [21]. Long lasting type 1 DM patients may susceptible
Type 2 diabetes mellitus to microvascular complications; [22-24] and macrovascular disease
The relative importance of defects in insulin secretion or in the (coronary artery, heart, and peripheral vascular diseases) [25].
peripheral action of the hormone in the occurrence of DM2 has been
and will continue to be cause for discussion. DM2 comprises 80%
Clinical features of Type II diabetes
to 90% of all cases of DM. Most individuals with Type 2 diabetes Most cases are diagnosed because of complications or incidentally.

2000 2030
Country People with People with
Ranking Country
diabetes (millions) diabetes (millions)
1 India
India 31.7 79.4
2 China
China 20.8 42.3
3 U.S.
U.S. 17.7 30.3
4 Indonesia
Indonesia 8.4 21.3
5 Pakistan
Japan 6.8 13.9
6 Brazil
Pakistan 5.2 11.3
7 Bangladesh
Russian Federation 4.6 11.1
8 Japan
Brazil 4.6 8.9
9 Philippines
Italy 4.3 7.8
10 Egypt
Bangladesh 3.2 6.7

Table 1: List of countries with the highest numbers of estimated cases of diabetes for 2000 and 2030. Adapted from Wild S [5].

J Diabetes Metab Volume 6 • Issue 5 • 1000541

ISSN: 2155-6156 JDM, an open access journal
Citation: Baynes HW (2015) Classification, Pathophysiology, Diagnosis and Management of Diabetes Mellitus. J Diabetes Metab 6: 541.
doi:10.4172/2155-6156.1000541

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I. type 1Diabetes mellitus

A. Autoimmune
B. Idiopathic
II. type 2 Diabetes mellitus
Ranges from relative insulin deficiency to disorders
3. Nicotinic acid
of insulin secretion and insulin resistance
4. Glucocorticoids
III. Other specific types of diabetes mellitus
5. Thyroid hormones
A. Genetic defects in β-cell function
6. Diazoxide
1. Chromosome 12, HNF-1α (MODY 3)
7. β-adrenergic agonists
2. Chromosome 7, glycosidase (MODY 2)
8. Tiazides
3. Chromosome 20, HNF-4α (MODY 1)
9. Dilantin
4. Mitochondrial DNA
10. α interferon
5. Monogenic diabetes
ii. Infections
B. Genetic defects in insulin action
1. Congenital rubeola
1. Type A insulin resistance
2. Cytomegalovirus
2. Leprechaunism
iii. Infrequent forms of autoimmune diabetes
3. Rabson-Mendenhall syndrome
1. Stiff-man syndrome)
4. Lipotrophic diabetes
2. Antibodies against insulin receptors
C. Disease of the exocrine pancreas
iv. Other syndromes occasionally associated with diabetes
1. Pancreatitis
1. Down syndrome
2. Pancreatectomy/trauma
2. Klinefelter syndrome
3. Neoplasia
3. Turner syndrome
4. Cystic fibrosis
4. Wolfram syndrome
5. Hemochromatosis
5. Friedreich ataxia
6. Fibrocalcific pancreatopathy
6. Huntington’s chorea
D. Endocrinopathies
7. Lawrence-Moon-Biedel syndrome
1. Acromegaly
8. Myotonic dystrophy
2. Cushing syndrome
9. Porphyria
3. Glucagonoma
10. Prader-Willi syndrome
4. Pheochromocytoma
IV. Gestational diabetes mellitus
5. Hyperthyroidism
Occurs in mostly in women during gestation.
6. Somatostatinoma
7. Aldosteronoma
i. Pharmacologically or chemically induced
1. Vacor
2. Pentamidine
Table 2: Etiologic Classification of Diabetes Mellitus. Adapted from WHO and ADA [6,19].

Characteristic Type 1 Type 2 Monogenic

Genetics Polygenic Polygenic Monogenic
Age of onset
6 months to young adulthood Usually pubertal (or later)
Often post pubertal except
Glucokinase and neonatal diabetes
Clinical presentation Most often acute, rapid Variable; from slow, mild (often
Variable (may be incidental in
insidious) to severe
glucokinase)
Associations Yes No
No
Autoimmunity Common Uncommon
Common in neonatal diabetes, rare in
Ketosis
other forms
Population frequency
Population Increased frequency
Obesity
No
No Yes
Acanthosis nigricans
1-3%
Frequency Usually 90%+ Most countries
(% of all diabetes
90%
in young people) 2-4% 80%
Parent with diabetes
Table 3: Clinical characteristics of type 1 diabetes, type 2 diabetes and monogenic diabetes in children and adolescents. Adapted from Craig ME [29].

Carries a high risk of large vessel atherosclerosis commonly associated Type 1 diabetes mellitus
with hypertension, hyperlipidaemia and obesity. Most patients with
Type 1 Diabetes is characterized by autoimmune destruction of
type 2 diabetes die from cardiovascular complications and end stage insulin producing cells in the pancreas by CD4+ and CD8+ T cells and
renal disease. Geographical variation can contribute in the magnitude macrophages infiltrating the islets [31]. Several features characterize
of the problems and to overall morbidity and mortality [26-28] (Table type 1 diabetes mellitus as an autoimmune disease [32]:
3).
1. Presence of immuno-competent and accessory cells in infiltrated
Pathogenesis and Pathophysiology of Diabetes Mellitus pancreatic islets;

There is a direct link between hyperglycemia and physiological 2. Association of susceptibility to disease with the class II (immune
& behavioral responses. Whenever there is hyperglycemia, the brain response) genes of the major histocompatibility complex (MHC;
human leucocyte antigens HLA);
recognizes it and send a message through nerve impulses to pancreas
and other organs to decrease its effect [30]. 3. Presence of islet cell specific autoantibodies;

J Diabetes Metab Volume 6 • Issue 5 • 1000541

ISSN: 2155-6156 JDM, an open access journal
Citation: Baynes HW (2015) Classification, Pathophysiology, Diagnosis and Management of Diabetes Mellitus. J Diabetes Metab 6: 541.
doi:10.4172/2155-6156.1000541

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4. Alterations of T cell mediated immunoregulation, in particular Insulin resistance

in CD4+ T cell compartment;
The primary events are believed to be an initial deficit in insulin
5. The involvement of monokines and TH1 cells producing secretion and in many patients relative insulin deficiency in association
interleukins in the disease process; with peripheral insulin resistance [37]. Resistance to the action of
insulin will result in impaired insulin mediated glucose uptake in
6. Response to immunotherapy and; the periphery (by muscle and fat), incomplete suppression of hepatic
7. Frequent occurrence of other organ specific auto- immune glucose output and impaired triglyceride uptake by fat. To overcome
diseases in affected individuals or in their family members. the insulin resistance, islet cells will increase the amount of insulin
secreted. Endogenous glucose production is accelerated in patients
Approximately 85% of patients have circulating islet cell antibodies, with type 2 diabetes or impaired fasting glucose. Because this increase
and the majorities also have detectable anti-insulin antibodies before occurs in the presence of hyper insulinemia, at least in the early and
receiving insulin therapy. Most islet cell antibodies are directed against intermediate disease stages, hepatic insulin resistance is the driving
glutamic acid decarboxylase (GAD) within pancreatic B cells [33]. force of hyperglycemia of type 2 diabetes (Figure 1- 7).
The autoimmune destruction of pancreatic β-cells, leads to Complications of diabetes mellitus
a deficiency of insulin secretion which results in the metabolic
derangements associated with T1DM. In addition to the loss of insulin 1- Acute complications
secretion, the function of pancreatic α-cells is also abnormal and 1.1 Hypoglycemia
there is excessive secretion of glucagons in T1DM patients. Normally,
1.2 Hyperglycemic crises
hyperglycemia leads to reduced glucagons secretion, however,
in patients with T1DM, glucagons secretion is not suppressed by Diabetes Ketoacidosis (DKA)
hyperglycemia [34]. The resultant inappropriately elevated glucagons
Hyperglycemic hyperosmolar state (HHS)
levels exacerbate the metabolic defects due to insulin defi-ciency.
Although insulin deficiency is the primary defect in T1DM, there is 2- Chronic complications:
also a defect in the administration of insulin. Deficiency in insulin
2.1 Micro vascular complications
leads to uncontrolled lipolysis and elevated levels of free fatty acids
in the plasma, which suppresses glucose metabolism in peripheral 2.1.1 Diabetic retinopathy
tissues such as skeletal muscle [34]. This impairs glucose utilization 2.1.2 Diabetic nephropathy
and insulin deficiency also decreases the expression of a number of
genes necessary for target tissues to respond normally to insulin such 2.1.3 Diabetic neuropathy
as glucokinase in liver and the GLUT 4 class of glucose transporters in
adipose tissue [34] explained that the major metabolic derangements,
which result from insulin deficiency in T1DM are impaired glucose,
lipid and protein metabolism.
Type 2 diabetes mellitus
In type 2 diabetes these mechanisms break down, with the
consequence that the two main pathological defects in type 2 diabetes
are impaired insulin secretion through a dysfunction of the pancreatic
β-cell, and impaired insulin action through insulin resistance [35].
In situations where resistance to insulin predominates, the mass of
β-cells undergoes a transformation capable of increasing the insulin
supply and compensating for the excessive and anomalous demand.
In absolute terms, the plasma insulin concentration (both fasting and
meal stimulated) usually is increased, although “relative” to the severity
of insulin resistance, the plasma insulin concentration is insufficient to
maintain normal glucose homeostasis. Keeping in mind the intimate
relationship between the secretion of insulin and the sensitivity of
hormone action in the complicated control of glucose homeostasis, it is
practically impossible to separate the contribution of each to the etio-
pathogenesis of DM2 [20].
Insulin resistance and hyperinsulinemia eventually lead to impaired
glucose tolerance [36]. Except for maturity onset diabetes of the young
(MODY), the mode of inheritance for type 2 diabetes mellitus is
unclear. MODY, inherited as an autosomal dominant trait, may result
from mutations in glucokinase gene on chromosome 7p. MODY is
defined as hyperglycemia diagnosed before the age of twenty-five years
and treatable for over five years without insulin in cases where islet cell Figure 1: Physiologic and Behavioral response of hyperglycemia. Adapted from
Cryer [30].
antibodies (ICA) are negative [26].

J Diabetes Metab Volume 6 • Issue 5 • 1000541

ISSN: 2155-6156 JDM, an open access journal
Citation: Baynes HW (2015) Classification, Pathophysiology, Diagnosis and Management of Diabetes Mellitus. J Diabetes Metab 6: 541.
doi:10.4172/2155-6156.1000541

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Figure 2: Pathogenesis of type 1 diabetes.

Figure 4: Panel A shows the physiological effect of a decrease in insulin

coupled with a low glucose concentration in stimulating alpha-cell glucagon
secretion, and Panel B shows the pathophysiological effect of beta-cell failure
and the resulting loss of a decrease in insulin secretion and loss of an increase
in alpha-cell glucagon secretion, despite a low glucose concentration. Adapted
from Cryer [39].

Diagnosis of diabetes mellitus

The identification of patients with diabetes or pre-diabetes by
screening allows for earlier intervention, with potential reductions in
future complication rates, although randomized trials are lacking to
definitively show benefit. The patient described in the vignette has risk
Figure 3: Pathophysiology of Hyperglycemia and increased circulating fatty
acids in type 2 Diabetes. Adapted from Pittas [26]. factors (obesity, hypertension, and a family history of diabetes) and
should be screened (Table 4) [38-40]. About 25% of patients with type 2
DM already have microvascular complications at the time of diagnosis
2.2 Macrovascular disease suggesting that they have had the disease for more than 5 years at the
time of diagnosis [41,42]. As a result there are different approaches to
3- Other complications and associated conditions
diagnose diabetes among individuals.
3.1 Impaired growth and development
The 1997 American Diabetes Association (ADA) recommendations
3.2 Associated autoimmune conditions for diagnosis of DM focus on Fasting Plasma Glucose (FPG), while
3.2.1 Hypothyroidism WHO focuses on the Oral Glucose Tolerance Test (OGTT) [43] (Table
5).
3.2.2 Hyperthyroidism
Diagnosis of both types of diabetes
3.2.3 Celiac disease
Random plasma test
3.2.4 Vitiligo
• The simplest test and doesn’t require fasting before taking the
3.2.5 Primary adrenal insufficiency (Addison’s disease) test.
3.3 Lipodystrophy (lipoatrophy and lipohypertrophy)
• If 200 or more than 200 mg/dl of blood glucose it probably
3.4 Necrobiosis lipoidica diabeticorum indicates diabetes but has to be reconfirmed.
3.5 Non-alcoholic fatty liver disease
Fasting plasma glucose test:
3.6 Infections seen in patients with diabetes
• There should be eight hours fasting before taking this test. Blood
3.7 Limited joint mobility glucose more than 126 mg/dl on two or more tests conducted on
3.8 Edema different days confirms a diabetes diagnosis [43].

J Diabetes Metab Volume 6 • Issue 5 • 1000541

ISSN: 2155-6156 JDM, an open access journal
Citation: Baynes HW (2015) Classification, Pathophysiology, Diagnosis and Management of Diabetes Mellitus. J Diabetes Metab 6: 541.
doi:10.4172/2155-6156.1000541

Page 6 of 9

• Fasting glucose level is determined, and then gives 75 gm of

At risk patient glucose, 100 gm for pregnant women. The blood is tested every 30
minutes to one hr for two or three hrs.
Check FPG glycated hemoglobine or both every 2 year
• This test is normal if your glucose level at two hrs is less than 140
mg/dl. A fasting level of 126 mg/dl or greater and two hour glucose
level of 200 mg/dl or Higher confirms a diabetes diagnosis [43].
Normal IFG or IGH Diabetes suspected
Glycated proteins
Repeat screen in 1-3 yr Prediabetes Confirm Proteins react spontaneously in blood with glucose to form
glycated derivatives. The extent of glycation of proteins is controlled
by the concentration of glucose in blood and by the number of reactive
Life style change amino groups present in the protein that are accessible to glucose
Diabetes for reaction. All proteins with reactive sites can be glycated and the
Prediabetes
concentration of the glycated proteins that can be measured in blood is
a marker for the fluctuation of blood glucose concentrations during a
certain period. From a clinical diagnostic point glycated proteins with
Improved glycemia Stable glycemia Treatment a longer life time in blood are of interest, since they reflect the exposure
dependent on
degree of of these proteins to glucose for longer periods
hyperglycemia;if
Continue life style Continue life style Progressive mild begin with Glycated hemoglobin
change,check change, life style change
glycemia
FPG,glycated with or with out The life span of hemoglobin in vivo is 90 to120 days. During this
Check FPG,glycated notformins
hemoglobin or time glycated hemoglobin A forms, being the ketoamine compound
both in 12 hemoglobin or
months both in 6 months formed by combination of hemoglobin A and glucose. Several
Intensify efforts subfractions of glycated hemoglobin have been isolated. Of these,
Consider glycated hemoglobin A fraction HbA1c is of most interest serving as
metformins a retrospective indicator of the average glucose Concentration. HbA1c
is recommended as an essential indicator for the monitoring of blood
Figure 5: Suggested approach to screening patients at risk for diabetes.
Adapted from Salomaa and Diabetes Care [36,48].
glucose control. The blood HbA1c≥ 6.5% is considered as diabetes [44].

Hospitalized patient with hyperglycemia but not critically ill

Measure glycated hemoglobin

Patient with type I,type II or newly diagnosed Patient with type II diabetes on terapy

Patient eating Patient recieving Patient eating

Patient recieving
nothing by mouse nothing by mouse
Continue oral agents if no
Continue out patient regimen if contraindication and glucose
Glucose well controlled well controlled

Basal insulin dose If glucose not well Discontinue If poorly controlled

with 0.2-0.3 u/kg of controlled begin basal oral agents, discontinue oral
weight/day or 0.2-0.3 u/kg/day or begin for agents,begin basal
insuline every 12- insulin every 12-24 hr blood glucose insulin of 0.2-0.3
24hr plus : plus prandial insulin ≥ 150 mg/dl u/kg/day plus prandial
correctioninsulin 0.05-0.1 u/kg/meal of 1-4 u for insulin 0.05-
for blood glucose > plus correction insuline each 0.1u/kg/meal plus:
150mg/kg of 1-2 u for blood glucose≥ 150 increament correction insuline for
for each mg/dl of 1-4 u for of 50mg/dl blood glucose>150
increament of each increament of mg/dl of 1-4 u for each
50mg/dl 50mg/dl increament of 50mg/dl
If glucose level is not controlled make the following changes taking in to consideration other
factors that may be responsible for hyperglycemia
Figure 6: Schematic overview of the major areas contributing to diabetic
complications. Adapted from Josephine M [40]. Add basal insulin
Adjust basal insulin Add basal insulin adjust by 10-20%
Adjust basal insulin by
by 10-20 % every 1-2 0.2-0.3 u/kg/day every 1-2 days
10-20 % every 1-2 days
days adjust adjust by 10- adjust correction
Oral glucose tolerance test adjust correction insulin
correction insulin by 20% every 1-2 insulin by 1-2
by 1-2 u/dose every 1-2
1-2 u/dose every 1-2 days u/dose every 1-2
days
• When random plasma glucose test is 160-200 mg/dl and the days days
fasting plasma test is 110-125 mg/dl, then this test is conducted [7].
Figure 7: General management of diabetes mellitus. Adapted from Riddle
• This blood test evaluates body’s response to glucose. This test MC [63].
requires fasting at least eight but not more than 16 hrs.

J Diabetes Metab Volume 6 • Issue 5 • 1000541

ISSN: 2155-6156 JDM, an open access journal
Citation: Baynes HW (2015) Classification, Pathophysiology, Diagnosis and Management of Diabetes Mellitus. J Diabetes Metab 6: 541.
doi:10.4172/2155-6156.1000541

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1. Insulin resistance: usually associated with obesity between patients identified as having pre-diabetes by means of glycated
2.      Family history of T2DM in first- or second-degree relative hemoglobin testing and those identified by means of fasting plasma
3.      Ethnicity: African-American, Hispanic, Pacific Islander, Native glucose testing. Such risks probably vary according to which test is
American, Canadian First Nation
4.      Small size for gestational age (intrauterine growth restriction) used ultimately to make the diagnosis. Ongoing research is assessing
5.      Maternal gestational diabetes the value of risk scores that incorporate not only glycemic measures but
6.      Insulin resistance of puberty also other biomarkers and risk factors to estimate diabetes risk [46,47].
7.      Lack of physical activity
8.      High-calorie diet Impaired fasting glucose (IFG) is defined as a fasting plasma glucose
(FPG) level of 100 to 125 mg/dl (5.6 to 6.9 mmol/liter). Increased
Table 4: Risk factors for T2DM in youth. Adapted from Botero D [38]. glycated hemoglobin (IGH) is defined as a glycated hemoglobin level
of 5.7 to 6.4%. The diagnosis of diabetes is confirmed with a repeat test
Criteria:
*       Overweight and obese children
on a separate day or by the alternative test (i.e. glycated hemoglobin
o       BMI >85th percentile for age and sex instead of FPG or vice versa) on the same day or a separate day. If the
o       Weight for height >85th percentile result of the repeat test is in the prediabetic range, the patient should
o       Weight >120% of ideal for height be counseled or treated for pre-diabetes. If the result of the repeat test
Plus any two of the following risk factors: is entirely normal (which is unlikely), rescreening in 6 months should
a. Family history of T2DM in first or second-degree relative be considered.
b. Race/Ethnicity
* Native-American                    * Latino Glycemic Management
 * African-American * Asian American
* Pacific Islander                          One of the biggest challenges for health care providers today
c. Signs of insulin resistance or conditions associated with insulin resistance
* Acanthosis nigricans                  * Hypertension
is addressing the continued needs and demands of individuals
* Dyslipidemia                              * PCOS with chronic illnesses like diabetes [49]. The importance of regular
* Small for gestational age birth weight follow-up of diabetic patients with the health care provider is of
d. Maternal history of diabetes or GDM during the child's gestation great significance in averting any long term complications. Studies
Age of initiation:  age 10 years or at onset of puberty, if puberty occurs at a have reported that strict metabolic control can delay or prevent the
younger age progression of complications associated with diabetes [50,51]. Results
of large randomized trials involving patients with type 1 diabetes or
Frequency: every 3 years
newly recognized or established type 2 diabetes show that control of
Preferred Test: Fasting plasma glucose
Time Plasma Glucose
Table 5: Modified ADA Guidelines for screening children and youths for T2DM. ≥95mg/dl(5.3mmol/L)
Fasting
Adapted from ADA [42].
≥180mg/dl(10.0mmol/L)
1-hour
Fructosamine test
≥155mg/dl(8.6mmol/L)
Albumin is the main component of plasma proteins. As albumin 2-hour

also contains free amino groups, non-enzymatic reaction with glucose ≥140mg/dl(7.8mmol/L)
3-hour
in plasma occurs. Therefore glycated albumin can similarly serve as a
marker to monitor blood glucose. Glycated albumin is usually taken to Two or more values must be met or exceeded for a diagnosis of diabetes to be
made. The test should be done in the morning after 8 to 14 hours fast.
provide a retrospective measure of average blood glucose concentration
over a period of 1 to 3 weeks. Reference interval: 205- 285 micro mol/L. Table 6: Diagnosis of gestational diabetes.

Diagnosis of gestational diabetes mellitus Measure

American Diabetes World Health
Association Organization
At least 6 weeks after the pregnancy ends, the woman should Diabetes
receive an oral glucose tolerance test and be reclassified as having Diabetes Impaired
Prediabetes
diabetes, normal glucose tolerance, impaired
glucose
glucose tolerance or impaired fasting glucose (Table 6). Women ≥ 126 mg/dl 100-125
≥ 126 mg/dl 110-
125
at high risk (positive family history, history of GDM, marked obesity, Fasting plasma glucose mg/dl(IFG)
mg/dl
and high risk ethnic group) should be screened as soon as feasible. If (IFG)
the initial screening is negative, they should undergo retesting at 24-48 2-Hr plasma glucose
≥ 200 mg/dl 140-199 ≥ 200 mg/dl 140-
weeks. The diagnosis of GDM is made if two or more of the plasma (during
Mg/dl 199
An OGTT with a loading
glucose values in (Table 7) are met or exceeded [32]. dose
mg/dl
(IGT) (IGT)
Of 75 g
It is unclear whether the risk of complications of diabetes differs
Casual(random ) plasma
according to whether the disease was diagnosed by means of fasting glucose
plasma glucose testing only or glycated hemoglobin testing only. (In a patient with classic
≥ 200 mg/dl ≥ 200 mg/dl
Preliminary data from a large, community- based prospective cohort hyper
Glycemic symptom)
study suggest that the glycated hemoglobin level, which integrates
Glycated hemoglobin ≥ 6.5% 5.7-6.4% ≥ 6.5%
fasting and postprandial glucose levels over a longer period, might be
a better predictor of certain complications especially cardiovascular Table 7: Major diagnostic criteria for diabetes and prediabetic or at-risk states.
Data are adapted from the American Diabetes Association. Adapted from
disease [45]. It is also not known whether the risk of diabetes differs Salomaa and Diabetes Care [22,23].

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ISSN: 2155-6156 JDM, an open access journal
Citation: Baynes HW (2015) Classification, Pathophysiology, Diagnosis and Management of Diabetes Mellitus. J Diabetes Metab 6: 541.
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Page 8 of 9

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