Diabetes Mellitus

Etiologic classification of diabetes mellitus

DMI: destruction of the pancreatic beta cells, leading to absolute insulin deficiency

A: autoimmune (GAD65, ICA, insulin, Tyrosine phosphatase 1A2 or 1A2B)
B: idiopathic
DMII (may range from predominantly insulin resistance with relative insulin
deficiency to a predominantly secretory defect with insulin resistance)
Other specific types
A. Genetic defects of beta cell function (MODY)
B.Genetic defects in insulin action
C. Diseases of the exocrine pancreas (pancreatitis, CF, Hereditary hemochromatosis)
D. Endocrinopathies: (acromegaly, Cushing's Syndrome, Glucagonoma, Pheochromocytoma,
Hyperthyroidism, Somatostatinoma
E. Drug- or chemical-induced (OCP, Steroids, cyclosporine )
F. Infections (CMV)
G. Uncommon forms of immune-mediated diabetes (stiff-person Syn)
H. Other genetic syndromes sometimes associated with diabetes (Down's Syn, Turner's Syn
Gestational diabetes mellitus (GDM)

Distinguishing DMI from DMII
We often measure autoantibodies (GAD65, insulin, tyrosine phosphatases [IA-2 and
IA-2], islet cell) when the diagnosis of type 1 or type 2 diabetes is uncertain by
clinical presentation (ie, thin patient with poor response to initial therapy with
sulfonylureas or metformin , personal or family history of autoimmune disease). If
one or more of the antibodies is present, and especially if two or more are positive, the
patient should be presumed to have type 1 diabetes and should be treated with insulin
replacement therapy.
Clinical features Type1 DM Type2 DM MODY
Age Majority <25, but may occur
at any age
Typically >25 <25
Weight Usually thin >90 percent at least overweight Similar to general population
autoantibodies Present Absent Absent
Insulin dependent yes no No
Insulin sensitivity Normal when controlled Decreased Normal (may be decreased if
obese)
Family history of
diabetes
Infrequent (5 to 10 percent) Frequent (75 to 90 percent) Autosomal dominant
Risk of diabetic
ketoacidosis
High low low
Screening for DM
Routine screening for type 1 diabetes is not recommended.
For patients with risk factors for type 2 diabetes, we suggest screening:
Candidates for screening include adults with a BMI 25 kg/m2 who have
one or more additional risk factors for diabetes (eg, family history
diabetes mellitus in a first-degree relative, habitual physical inactivity,
gestational diabetes, hypertension, dyslipidemia). For adults without risk
factors, we suggest that screening begin at age >45 years
Either glycated hemoglobin (A1C), fasting plasma glucose (FPG), or 2-h 75 g
OGTT are appropriate screening tests.
In patients with normal A1C or FPG, we suggest a follow-up measurement in
three years
Patients meeting the criteria for diagnosis of diabetes or increased risk for
diabetes should be counseled vigorously on issues related to lowering their
risk of macrovascular disease (smoking cessation, use of aspirin , diet, and
exercise), and should have measurements of blood pressure and serum lipids.

Criteria for the diagnosis of diabetes
1. A1C 6.5 percent. The test should be performed in a laboratory using a method that is NGSP
certified and standardized to the DCCT assay.
OR
2. FPG 126 mg/dL (7.0 mmol/L). Fasting is defined as no caloric intake for at least 8 h.*
OR
3. Two-hour plasma glucose 200 mg/dL (11.1 mmol/L) during an OGTT. The test should be
performed as described by the World Health Organization, using a glucose load containing the
equivalent of 75 g anhydrous glucose dissolved in water.
OR
4. In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma
glucose 200 mg/dL (11.1 mmol/L).

* In the absence of unequivocal hyperglycemia, criteria 1-3 should be confirmed by repeat
testing.
Categories of increased risk for diabetes (prediabetes)
FPG 100 to 125 mg/dL (5.6 to 6.9 mmol/L) [IFG]
2-h PG on the 75-g OGTT 140 to 199 mg/dL (7.8 to 11.0 mmol/L) [IGT]
A1C 5.7 to 6.4 percent


Distinguishing DMI from DMII
We often measure autoantibodies (GAD65, insulin, tyrosine phosphatases [IA-2 and
IA-2], islet cell) when the diagnosis of type 1 or type 2 diabetes is uncertain by
clinical presentation (ie, thin patient with poor response to initial therapy with
sulfonylureas or metformin , personal or family history of autoimmune disease). If
one or more of the antibodies is present, and especially if two or more are positive, the
patient should be presumed to have type 1 diabetes and should be treated with insulin
replacement therapy.

Screening and diagnosis of diabetes mellitus
during pregnancy
Definitions:
Overt diabetes: any of the following criteria at initial prenatal visit:
Fasting plasma glucose 126 mg/dL [7.0 mmol/L], or
A1C 6.5 percent using a standardized assay, or
Random plasma glucose 200 mg/dL [11.1 mmol/] that is subsequently
confirmed by elevated fasting plasma glucose or A1C, as described above
Gestational diabetes: either of the following criteria
Fasting plasma glucose 92 mg/dL [5.1 mmol/L], but <126 mg/dL [7.0
mmol/L] at any gestational age
At 24 to 28 weeks of gestation: 75 gram two hour oral glucose tolerance test
(GTT) with at least one abnormal result: fasting plasma glucose 92 mg/dL
[5.1 mmol/L], but <126 mg/dL [7.0 mmol/L] or one hour 180 mg/dL (10.0
mmol/L) or two hour 153 mg/dL (8.5 mmol/L)
Screening
We suggest screening for diabetes during pregnancy
We suggest universal screening, rather than selective screening based upon
risk factors.We obtain an A1C level at the initial prenatal visit. If <6.5 percent,
we perform a 75 gram two hour oral GTT at 24 to 28 weeks of gestation.

A two step approach (ie, a 50 gram glucose challenge screening test at 24 to
28 weeks followed by a 100 gram three hour oral GTT) in screen positive
patients (glucose 130 or 140 mg/dL [7.2 or 7.8 mmol/L]) is also an
acceptable approach. (considered positive when 3hour OGTT140-145)

Overview of medical care in adults with diabetes mellitus
Morbidity from DM is a consequence of both macrovascular disease (atherosclerosis)
and microvascular disease (retinopathy, nephropathy, and neuropathy). these
complications can be slowed, but probably not stopped.
Every visit Smoking BP The other risk
factors
Lifestyle change
Target
140/80
Every 3-6 Mo A1C
Anually Dilated fundus Examination
*
UACR (30mcg/mg)
* &

Anually Comprehensive Foot examination Fasting lipid profile
Anually Creatinine (often)
**
Influenza vaccine
One time Pneumococcus + hepatitis B (3 doses) vaccines
*
Begin at onset of type 2 diabetes, three to five years after onset of type 1 diabetes.
&
abnormal results should be repeated at least 2-3 times over a 3-6 months
** All patients with UACR positive or taking metformin
Give aspirine (81mg) for patients over 50(males) or 60 (Females) who have another
CVD risk factor
Dyslipidemia: Targets: LDL<100 TRIG<150 HDL> 40 or 50 (men or women)
Start with lifestyle intervention, add Statin if LDL>100 persists. Start statin with
lifestyle intervention in patients> 40 years and have another Risk factor for CVD.
Women of childbearing age: ADA guidelines: use the same guidelines that apply to
women without DM. ACOG guidelines: recommend that use of OCP be limited to
nonsmoking diabetic women who are younger than 35 years and are without
hypertension, nephropathy, retinopathy, or other vascular disease
A1C Target is <7% (generally) which is usually achieved with FPG 70-130 and
postprandial Glucose (after 2 hour) <180
Prediabetes Patients
Lifestyle change, Weight reduction (5-10%), Physical exercise of at least
150min/week and smoking cessation.
Consider Metformin therapy, particularly in patients who are <60 years of age,
have a BMI 35 kg/m2, or in women with prior gestational diabetes