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Endocrine Subspeciality October 8 2009 Dr Onyemere Dr Kapoor PGY3.

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Presentation on theme: "Endocrine Subspeciality October 8 2009 Dr Onyemere Dr Kapoor PGY3."— Presentation transcript:

1 Endocrine Subspeciality October 8 2009 Dr Onyemere Dr Kapoor PGY3

2 Case  19 year old African American gentleman.  Presents to the ED with complains of nausea for 2 days  Complaining of polyuria, polydipsia and polyphagia.  No complains of fever, chills.  No complains of chest pain, cough, shortness of breathe.  No complains of diarrhea, constipation, abdominal pain.  No complains of urinary complains.

3  Past medical history None, no hospitalizations.  Social history Never smoked, no history of alcohol abuse.  Family history Grand mother having history of diabetes. No history of DM in parents.  Medications None  Allergy None

4 Case contd  On examination BP- 101/52, Pulse – 105, RR – 20, afebrile Gen – Alert, orientedx3, not in any apparent distress. Mucus membranes are dry. HEENT – PERRLA, EOMI, No neck swelling. Acanthosis on the lateral aspect of his neck on either side. Chest – Air entry bilaterally equal and adequate, no wheezing, no crepitations CVS – S1,S2 normal regular Abdomen – Soft, non tender, non distended, BS present Extremities – No pedal edema, PPP CNS no focal deficits present

5 Case contd  Labs WBC – 14.9, hemoglobin – 17.7, platelet – 226. Calcium 10.2 Na 135 K 5.6 Chloride 95 Bicarb – 24 Bun 18 Creatinine 1.6 Total protein 8.2, Albumen – 4.1 Glucose – 864 Urinalysis – Glucose 1000, Specific gravity – 1.027, Ketone 40, pH – 5.0, ABG – 7.315, 44,74,22,fio2 21. Hb a1c – 13.5

6 Management  Patient was given 10 units bolus and then started on insulin drip.  Patient was given IV NS bolus and followed by D5 ½ NS to control the ketosis.  Blood glucose levels were controlled and after ketosis and acidosis were resolved, patient was started on scheduled insulin.  Started on PO diet.  Patient was then discharged on Lantus 50 units QAM, Aspart 18-20-20-0 with meals.

7 Diagnosis  Patient was discharge home with the diagnosis of ?????

8 IS it Type 1 or type 2 DM What do you think….

9 Ketosis prone DM type 2  First described in 1987 by Winter et al.  Was earlier called Atypical diabetes.  Have been described mostly in African, African American, Hispanic and Native American Population.

10  Diabetes is these patients is characterised by an acute presentation, an autosomal dominant pattern of inheritance, negative islet-cell antibodies, and an insulin response to mixed meals that was intermediate between that seen in non-diabetic controls and in patients with type 1 diabetes.  Studies have been done showing measurable pancreatic insulin reserve, absence of autoimmune indicators of beta cell destruction, and increased frequency of HLA-DR3 and HLA DR4.  It was shown that many people with ketosis-prone type 2 diabetes have a severe but transient defect in insulin secretion and insulin action, which partially resolves after a few weeks of insulin therapy and is followed by near-normoglycemic remission that may last for months to years.

11 Pathogeneisis  The function of the cells was assessed by changes in levels of insulin and C-peptide during a 20-hour glucose infusion (200 mg/m2 per min), and a 48-hour infusion of Intralipid plus heparin infusion (250 U/h) to increase levels of free fatty acid in obese patients.  Dextrose infusion rapidly increased levels of Cpeptide by 4- to 5-fold during the first 10 hours; thereafter, insulin secretion progressively decreased.  After 20 hours of glucose infusion, levels of insulin and C- peptide were lower than preinfusion baseline levels.  However, increasing free fatty acid levels by 3-fold during the 48-hour Intralipid and heparin infusion was not associated with a deleterious effect on insulin secretion.  Chronic hyperglycemia induces a generalized downregulation of the glucose-processing system that leads to impaired -cell function and insulinopenia.

12 Pathogenesis  Down regulation of AKT2 expression in the muscle which helps in the phosphorylation has been described with chronic hyperglycemia.  This explained the reduction in the insulin sensitivity during the hyperglycemia episodes in patients with ketosis prone DM2.

13 Clinical presentation  Most patient are adults, obese, middle age with newly diagnosed diabetes and present with unprovoked diabetic keto acidosis.  Initial presentation is acute. History of polyuria, polydipsia and wright loss for less than 4 to 6 weeks.  Mean age of diagnosis is 40 years.  More prevalent in men.  Patient may have signs of dehydration, dry mucous membranes and tachycardia.  The severity of the glucose elevation and acidosis is similar to the patient with DM I and ketoacidosis.

14 Clinical course Various studies have shown 42 percent of the patient achieve remission ( A1C < 6.3 and fasting blood glucose < 120mg/dl.) in 83 days and stayed in remission at 20 months. African American patients tend to respond better. Patient with DKA who have achieved remission should be continued on sulfonyluria and metformin maintain remission for a longer duration.

15 Immunological studies  The prevalence of auto antibodies in obese African- American patients with DKA ( 17 percent ) is similar to that in obese patients with non ketotic hyperglycemia ( 17 percent )but is substantially lower than in lean patients with type 1 diabetes who have DKA. ( 66 percent )  The rate is similar to that reported in patients with type 2 diabetes.  This subset is also called slowly progressing Type 1 diabetes.  They tend to have considerably reduced basal and stimulated insulin secretion and tend to be more likely to relapse into hyperglycemia and be insulin dependent.

16 Factors predicting future near normoglycemic remission in adults with DKA  African-American, Hispanic, and other minority groups  Newly diagnosed diabetes  Obesity  Family history of type 2 diabetes  Negative autoantibodies (islet cells or glutamic acid decarboxylase)  Fasting C-peptide levels 0.33 nmol/L within 1 week after resolution of diabetic ketoacidosis or 0.5 nmol/L during follow-up.  Glucagon-stimulated C-peptide level 0.5 nmol/L at presentation and 0.75 nmol/L during follow-up

17 Glucagon stimulation test  After a 10 hour over night fast, blood samples are drawn at baseline and then at 3 or 6 mintues after injection of glucagon ( 1mg ) to measure levels of glucose and C-peptide.  These tests are done within 1 week of DKA and then 6-8 weeks of follow up.

18 Treatment  Initial insulin orders An initial intravenous bolus at 0.1 U/kg of body weight, followed by continuous insulin infusion at 0.1 U/kg per h. When blood glucose levels are 13.8 mmol/L (250 mg/dL), change intravenous fluids to 5% dextrose and 0.45% saline and reduce the insulin infusion rate to 0.05 U/kg per h to keep glucose levels at approximately 11.1 mmol/L (approximately 200 mg/dL) until resolution of ketoacidosis.

19  After the resolution of diabetic ketoacidosis Start multidose insulin at a dose of 0.8 U/kg of body weight. Adjust insulin dose to achieve target fasting and premeal glucose levels 6.6 mmol/L (120 mg/dL). Monitor patients every 2 weeks for the first 2 months to adjust insulin therapy, then every 2 or 3 months depending on glycemic control. The mean insulin requirement to achieve the target blood glucose level is usually 1 to 1.2 U/kg of body weight. Start tapering insulin once fasting blood glucose levels are 6.6 mmol/L (120 mg/dL) for 2 weeks or if the patient experiences hypoglycemia. Decrease total insulin dose by 25% at each visit. Measure GAD antibodies and Beta-cell function (fasting C- peptide or glucagon-stimulated C-peptide test).

20  After discontinuation of insulin therapy For patients with negative GAD and with fasting or stimulated C-peptide levels 0.5 nmol/L and 0.75 nmol/L, respectively, start therapy with low-dose sulfonylurea (glyburide, 1.25–2.5 mg/d) or metformin (500 mg twice per day). Patients with positive GAD or with inadequate insulin secretion are more likely to relapse. Insulin therapy may be continued, and patients should be carefully monitored for recurrence of hyperglycemia or ketosis.

21 Differential diagnosis  Maturity onset Diabetes of the young Autosomal dominant form of diabetes, which usually develops during childhood, adolescence, or young adulthood. It most commonly occurs in white and South Asian persons and is rare in African-American persons. The predominant physiologic feature is a defect in insulin secretion caused by mutations in the glucokinase gene or mutations of transcription factors that regulate expression of the insulin gene and insulin production. Most patients with maturity-onset diabetes of the young do not require insulin and can be treated with oral hypoglycemic agents, such as sulfonylureas.

22 Differential diagnosis  Tropical Fibrocalulous Diabetes Reported in the tropical areas of Asia, Africa, and South America. The clinical syndrome consists of a triad of chronic painful pancreatitis, malabsorption, and steatorrhea due to pancreatic exocrine insufficiency, along with diabetes mellitus. Patients’ histories frequently include chronic caloric and protein malnutrition. Pancreatic calculi can be detected in more than 90% of patients. Tropical diabetes is usually severe and often must be controlled with insulin; however, patients rarely become ketotic after insulin is withdrawn.


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