Dept of Diabetes and Endocrinology, Connolly Hospital, Blanchardstown Diabetes Mellitus Prof Seamus Sreenan Dept of Diabetes and Endocrinology, Connolly Hospital, Blanchardstown Mini Med School November 30th, 2011

Learning Objectives At the end of this talk you should understand: What diabetes mellitus means The difference between types-1 and -2 diabetes How the different types are treated The reasons for the current epidemic of diabetes and how it can be prevented What the complications of diabetes are and how they can be prevented

What is Diabetes? Diabetes Mellitus (sugar diabetes) is a disease characterized by high levels of sugar (glucose) in the blood Fasting glucose ≥ 7.0 (mmol/L)

Blood sugar and health Sugar (glucose) is an important source of energy Insulin is produced by the pancreas when blood sugar is high What is eaten is absorbed into the blood Insulin keeps blood sugar level within the normal range for health

Islet of Langerhans: Pancreas contains insulin-making cells in “islets” Insulin b-cells

Diabetes in a ‘nutshell’ Insufficient insulin to meet the body’s needs Either a complete lack (type 1) or relative lack (type 2) Results in raised blood glucose levels Untreated diabetes results in short-term symptoms and serious long-term complications Treatment aims to keep blood glucose levels as close to the normal range as safely possible Aim: Very basic introduction to diabetes for an audience that may not know a great deal about the disease area. NB can refer them back to their press packs which have detailed background information on diabetes and complications

Complications of Diabetes Short term: Symptoms of diabetes Dehydration Diabetic Coma Infections Long term: Kidney Eye Heart Circulation Amputation

Symptoms of Diabetes People with diabetes often have typical complaints (symptoms): Thirst and frequent drinking More frequent urination, particularly at night Unexplained weight loss Fatigue Blurred vision Frequent infections : skin, genital

Case 1 JN 32 year old male Referred to Emergency Dept by GP Complaining of thirst, excessive urination, half stone weight loss in the last 6 weeks No relevant past history First cousin has diabetes on insulin On no regular medications Thin man Blood sugar level = 24.7 mmol/L

What type of diabetes does JN have? There are 2 main types of diabetes: Type 1 (15%): Due to total lack of insulin – insulin treatment is required for life Type 2 (85%): Plenty of insulin which does not work very well in the body. Insulin treatment may be required at some stage but is not required in all patients

Differences between type-1 and type-2 Diabetes Mellitus Young age Normal BMI, not obese No immediate family history Short duration of symptoms (weeks) Can present with diabetic coma (diabetic ketoacidosis) Insulin required Type 2 Middle aged, elderly Usually overweight/obese Family history usual Symptoms may be present for months/years Do not present with diabetic coma Insulin not necessarily required Previous diabetes in pregnancy These differences are not absolute

JN Young age Thin No immediate family history Short duration of symptoms Insulin treatment required All point to probable type-1 diabetes

The Miracle of Insulin Patient J.L., December 15, 1922 February 15, 1923

Treatment of Type-1 Diabetes Mellitus: Insulin must be administered into the subcutaneous pocket between fat & muscle & avoid injection into fat or muscle. Can be administered by needle and syringe or by pen device

Alternative way to deliver insulin treatment: Continuous insulin infusion (insulin pump)

Islet replacement treatment Aim to replace the need for insulin treatment (Kidney) Pancreas transplantation Islet transplantation – not available in Ireland Anti-rejection drugs required Stem cell transplantation - experimental

Case 2 Ms AJ, a 45 year old woman is concerned she may have diabetes She had diabetes during her last pregnancy managed with diet Lately she has been feeling tired but otherwise has no complaints Her mother and one of her two sisters already have diabetes treated with tablets She has been overweight since her last pregnancy and has taken a tablet for blood pressure for the last 2 years She is obese, body mass index 34.5 Blood pressure is 140/90 but otherwise her examination is normal She undergoes a testing and her fasting glucose is 9.4 mmol/L Obese, strong family history, aged in 40s, previous history of diabetes in pregnancy all point to type-2 diabetes

Natural History of Type 2 Diabetes Normal Prediabetes Type 2 diabetes Insulin resistance Increasing insulin resistance Insulin secretion Hyperinsulinemia, then islet cell failure There is a temporal relationship between insulin resistance, insulin secretion and the development of diabetes. In the early stages, as insulin resistance rises, there is a compensatory increase in insulin secretion and the individual remains normoglycemic. In the long term, as the b-cells begin to fail, insulin secretion falls, abnormal glucose tolerance and hyperglycemia become apparent and frank type 2 diabetes develops. International Diabetes Center (IDC), Minneapolis, Minnesota. After meal glucose Abnormal glucose tolerance Fasting glucose High sugar levels Adapted from International Diabetes Center (IDC), Minneapolis, Minnesota.

Treatment of Type-2 Diabetes Diet/ exercise Oral monotherapy Oral combination Oral +/- insulin Insulin Diet and exercise my control condition for some time Variety of tablets available when diet exercise no longer work Tablets can be used in combination with each other or with insulin Insulin can also be used alone Stepwise approach The traditional stepwise approach aims primarily to control acute symptoms. Dietary measures and exercise are not usually sufficient to control glycemia beyond the first year of therapy. If oral monotherapy proves inadequate, combination therapy is usually started. If this also proves unsuccessful, conversion to insulin is the next step, either alone or in combination with an oral agent. In the majority of cases, the stepwise approach does not lead to sustained control. Many physicians intensify treatment only when symptoms of poor glycemic control become apparent, rather than when glycemic targets are not reached. Early, aggressive approach This approach to type 2 diabetes management avoids the risk of early treatment failure by adopting an intensive therapeutic strategy immediately upon diagnosis. Combinations of agents with complementary modes of action targeting the dual defects underlying type 2 diabetes (insulin resistance and b-cell dysfunction) are most likely to support tight, long-term glycemic control. Furthermore, combination therapy should be considered earlier in the regimen to provide additional glycemic control. Campbell IW. Br J Cardiol 2000; 7:625–631.

Prevalence of Diabetes Diabetes is very common It is becoming more common (particularly type-2) It affects about 200,000 Irish people 10% of the health budget spent on diabetes

Reason for increasing prevalence of type-2 diabetes The disease is reaching epidemic proportions because: Rates of overweight/obesity have increased We have become a physically inactive species Our diets are increasingly unhealthy

Everyone should know their BMI! Overweight and obesity are diagnosed by measuring weight and height (Body Mass Index (BMI)): Weight in Kg Height in metres2 Normal = 20-25 Overweight = 25-30 Obese = more than 30 Everyone should know their BMI! BMI =

Can Diabetes be Prevented? To be able to prevent a disease we need to be able to indentify people at particular risk of developing it

Risk factors for type 2 diabetes Certain people are more at risk of diabetes: Those who are overweight/obese People with a family history of diabetes Women who had diabetes during pregnancy or have had a baby weighing more than 9lbs Physically inactive people Certain ethnic groups (african, american indian, asian) People who have high blood pressure or high cholesterol Age more than 45 years

Can Diabetes be Prevented? Risk of Type 2 Diabetes can be reduced: Losing weight Taking regular exercise : walking for 30 mins per day Eating healthier food:  Less fat (burgers, fries, crisps, sweet foods)  More fibre (fruit and vegetables, wholegrain alternatives for rice, bread) Cutting down on alcohol consumption Ultimate aim is to reduce the longterm complications

Can the longterm complications be prevented? Type-1 1993: Study showed for the first time that good sugar control can prevent long term complications affecting eyes/kidneys/nerves Type-2 1998: Similar study showed same conclusion for type-2 Important therefore to know that sugar control is good and monitor frequently

Diabetes Mellitus: Self Monitoring SMBG Patients can draw blood frequently to monitor their glucose levels. A glucose monitor is used to check the sugar as required

Glycosylated Hemoglobin: HbAlc Blood test that measures the amount of glucose that has been incorporated into the hemoglobin protein of the red blood cell (RBC). Reflects the lifespan of a RBC, so test will reveal the effectiveness of diabetes therapy for the preceding 8-12 weeks. HbA1c levels remain more stable than sugar levels. Not affected by short-term fluctuations in sugar Normal is 4-6% Evaluated periodically (1-2 per year if well controlled, more frequently if not)

A1c and relative risk of complications (type 1 diabetes) : 20 Retinopathy Nephropathy Neuropathy Microalbuminuria 15 13 Aim for AIc of < 7% 11 9 Relative Risk (%) 7 5 3 Aim: To show why A1c control is important relating level to complications: Good glycaemic control is essential to reduce the risk of diabetic complications Based on the Diabetes Control and Complications Trial data that compared conventional with intensive regimens, the relative risk for microvascular complications such as diabetic retinopathy, nephropathy, neuropathy, and microalbuminuria increases with increasing levels of A1C1-3 The relative risk of complications is set to “1” for an A1C of 6%1 It is important to note that the risk gradient is continuous with no glycaemic threshold for developing complications1 1 6 7 8 9 10 11 12 A1c (%) DCCT, Diabetes Control and Complications Trial. 1. Adapted from Skyler JS. Endocrinol Metab Clin North Am. 1996;25:243-254. 2. DCCT. N Eng J Med. 1993;329:977-986. 3. DCCT. Diabetes. 1995;44:968-983. 1. Skyler JS. Diabetic complications: the importance of glucose control. Endocrinol Metab Clin North Am. 1996;25:243-254. 2. The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitis. N Engl J Med. 1993;329:977-986. 3. Diabetes Control and Complications Trial Research Group. The relationship of glycemic exposure (HbA1C) to the risk of development and progression of retinopathy in the Diabetes Control and Complications Trial. Diabetes. 1995;44:968-983.

How to prevent the complications Factors other than blood sugar increase likelihood of complications and should be managed Complications can be delayed/prevented by: Controlling blood sugars: sticking to diet/exercise programme, taking medication as prescribed Controlling blood pressure: diet, salt restriction, medication Controlling cholesterol levels: diet, statin tablets Stopping smoking Taking aspirin?

Useful websites Diabetes Federation of Ireland: www.diabetes.ie American Diabetes Association www.diabetes.org Irish Nutrition and Dietetic Institute www.indi.ie Juvenile Diabetes Research Foundation www.jdrf.org