REVIEW PRESENTATION

1
What do we know about diabetes as far as the
evidence goes

• REVIEW PRESENTATION
• RAQUEL GAROFANO
• R4 MFYC AXARQUÍA

2

• The word diabetes refers to a group of
  disorders with a number of common features, of
  which raised blood glucose is the most evident.
• ? Type 1 diabetes
• ? Type 2 diabetes
• ? Gestational diabetes (diabetes of pregnancy).

3
DIABETES TYPE 1
4
DEFINITION

• A condition of deficiency of insulin secretion
  from the pancreas, usually due to auto-immune
  damage of the insulin producing cells.
• The clinical condition is generally recognized on
  the basis of
• -----diabetes (high blood glucose levels)
  occurring in mainly younger and thinner people.
• -----in the absence of other precipitating causes.

• WORLD HEALTH ORGANIZATION

5
DIABETES TYPE 2

• A degree of high plasma glucose levels sufficient
  to put the individual at risk of the specific
  (microvascular) complications of diabetes.
• If they do not have Type 1 diabetes or other
  medical conditions or treatment suggestive of
  secondary diabetes.
• WORLD HEALTH
• ORGANIZATION

6
DRAFTING RECOMMENDATIONS

• Ia Evidence from meta-analysis of randomised
  controlled trials.
• Ib Evidence from at least one randomised
• controlled trial.
• IIa Evidence from at least one controlled study
  without randomisation.
• IIb Evidence from at least one other type of
  quasi-experimental study.

• A

B
7
DRAFTING RECOMMENDATIONS

• C

• III Evidence from non-experimental descriptive
  studies, such as comparative studies, correlation
  studies and case control studies.
• IV Evidence from expert committee reports or
  opinions and/or clinical experience of respected
  authorities.
• DS Evidence from diagnostic studies.
• NICE Evidence from NICE guidelines or health
  technology appraisal programme.

D
DS
NICE
8
DIAGNOSIS- D

• Single diagnostic laboratory glucose measurement
  over 200 mg / dl SYMPTOMS. ( Weight lost,
  increase in urinary frequency , polydipsia)
• Two diagnostic laboratory glucose measurements
  of
• -Fasting glucosegt126 mg /dl
• -Glucose two hours after 75 mg of glucose intake
  gt 200 mg / dl
• -HbA1 gt 6.5
• TYPE 1
• Specific auto-antibodies.
• Measure of C-peptide deficiency

9
CARE PROCESS-D

• INDIVIDUAL CARE PLAN
• Diabetes education.
• (Nutritional advice)
• Insulin therapy.
• Self-monitoring of glucose.
• Arterial risk factor assestmment and management.
• Means and frequency of communication with the
  professional care team.
• Follow-up consultations including next annual
  review

10
DIABETES EDUCATION

• Programme of structured diabetes education
  covering all major aspects of diabetes
  self-care A
• Flexible so that they can be adapted to
  specific educational, social and cultural
  needs D
• Designed and delivered by members of the
  multidisciplinary diabetes team. D

11
SELF MONITORING OF GLUCOSE- D

• Self-monitoring skills should be taught close to
  the time of diagnosis.
• Self-monitoring results should be interpreted in
  the light of clinically significant life events.
• It should be performed using meters and strips
  chosen by adults with diabetes to suit their
  needs. (Low blood requirements, fast analysis
  times and integral memories.)
• Structured assessment of self-monitoring skills
  should be made annually.

12

• OPTIMAL SELF MONITORING FREQUENCY- D

• Characteristics of an individuals blood glucose
  control.
• The insulin treatment regimen.
• Personal preference in using the results to
  achieve the desired lifestyle.

13
OPTIMAL TARGETS- D

• pre-prandial blood glucose level of 70-130 mg/dl
• post-prandial blood glucose level of less than
• 180 mg/dl.

14
DIETARY MANAGEMENT

• Nutritional information sensitive to personal
  needs and culture. D
• Nutritional information should be offered
  individually. D
• It should include advice from professionals with
  specific and approved training. D
• The hyperglycaemic effects of different foods a
  person wishes to eat should be discussed in
• the context of the insulin preparations chosen
  to match those food choices. A

15
DIETARY MANAGEMENT-D

• The choice of content, timing and amount of
  snacks between meals or at bedtime should be
  agreed on the basis of informed discussion.
• Information should also be made available on
• Effects of different alcohol-containing drinks on
  blood glucose and calorie intake.
• Use of high-calorie and high-sugar treats.
• Use of foods of high glycaemic index.

16
DIETARY MANAGEMENT-D

• Modifications according to
• Excess weight and obesity.
• Underweight.
• Eating disorders.
• Raised blood pressure.
• Renal failure.

17
DIETARY RECOMMENDATIONS

• High-fibre, low glycaemic index sources of
  carbohydrate in the diet, such as fruit,
  vegetables, wholegrains include low-fat dairy
  products and oily fish and control the intake of
  foods containing saturated and trans fatty acids.
• Target, for people who are overweight, an initial
  body weight loss of 15 .
• Discourage the use of foods marketed specifically
  for people with diabetes.

18
PSHYSICAL ACTIVITY

• It can reduce their enhanced arterial risk in the
  medium and longer term. C
• They should be offered information about D
• Appropriate intensity and frequency of physical
  activity.
• Role of self-monitoring of changed insulin and/or
  nutritional needs.
• Effect of activity on blood glucose levels when
  insulin levels are adequate. ( Likely fall ).

19
PHISICAL ACTIVITY- D

• Effect of exercise on blood glucose levels when
  hyperglycaemic and hypoinsulinaemic appropriate
  adjustments of insulin dosage and/or nutritional
  intake for exercise and post-exercise periods,
  and the next 24 hours
• Interactions of exercise and alcohol

20
CLINICAL MONITORING OF GLUCOSE-D

• Clinical monitoring of blood glucose levels by
• high-precision DCCT-aligned methods of
  haemoglobin A1c (HbA1c) should be performed every
  26 months, depending on
• Achieved level of blood glucose control.
• Stability of blood glucose control.
• Change in insulin dose or regimen.

21
GLUCOSE CONTROL ASSESSMENT LEVELS

• Maintaining a HbA1c below 7.5 is likely to
  minimize their risk of developing diabetic eye,
  kidney or nerve damage in the longer term. B
• If there is evidence of increased arterial risk
  (raised albumin excretion rate, features of the
  metabolic syndrome, or other arterial risk
  factors), approaching lower HbA1c levels (for
  example, 6.5 or lower) may be of benefit to
  them. NICE
• When the target HbA1c levels are not reached in
  the individual- Any improvement is beneficial in
  the medium and long term.B

22
TREATMENT
23
ORAL GLUCOSE LOWERING DRUGS

• should generally not be usedin the management of
  adults with type 1 diabetes
• D

24
ORAL GLUCOSE CONTROL THERAPIES

• Metormine
• secretagogues
• acarbose

25
METFORMINE-Ia

• Greater benefit than chlorpropamide,
  glibenclamide, or insulin for any
  diabetes-related outcomes, and for all-cause
  mortality.
• Overweight participants assigned to intensive
  blood glucose control with metformin showed a
  greater benefit than overweight patients on
  conventional treatment.
• Monotherapy with metformin produced significantly
  greater improvements in glycaemic control (i.e.
  HbA1c and FPG/fasting blood glucose (FBG)) when
  it was compared with placebo, diet and
  sulfonylureas.

26
METFORMINE-Ia

• Significant difference in terms of body
  weight/BMI reduction favouring metformin
  monotherapy when compared with sulfonylureas,
  glitazones and insulin therapies.
• Non-significant differences in terms of lipid
  profile were found when metformin was compared
  with placebo or metiglinides.
• When compared to diet, metformin significantly
  reduced total cholesterol (TC).

27
METFORMINE

• When compared to an a-glucosidase inhibitor,
  metformin significantly increased TC.Ia
• In a comparison of metformin against insulin,
  significant benefits for metformin were found in
  terms of total and LDL-C levels but not
  high-density lipoprotein cholesterol (HDL-C). Ia

28
INSULINE SECRETAGOGUES-Ia

• Metiglinides (repaglinide and nateglinide) vs
  placebo
• Produced a significantly greater glycaemic
  control and a higher incidence of hypoglycaemic
  events when compared with placebo.
• No differences were found in terms of body
  weight and lipid profile.

29
INSULINE SECRETAGOGUES-Ia

• Repaglinide vs nateglinide
• Repaglinide was more effective than nateglinide
  in reducing HbA1c and FPG values.
• A greater weight gain was seen in
  repaglinide-treated patients.
• Hypoglycaemic events were more frequently
  reported by patients receiving repaglinide.

30
INSULINE SECRETAGOGUES-Ia

• Metiglinides vs sulfonylureas
• Metiglinides failed to demonstrate better
• glucose control and led to a similar number of
  hypoglycaemic events.
• No significant differences were observed in terms
  of lipid profile and body weight reduction.

31
INSULINE SECRETAGOGUES-Ia

• Gliclazide modified release version vs
  glimepiride
• Both interventions were equally effective in
  terms of glycaemic control (alone or in
  combination with metformin or alpha-glucosidase
  inhibitors).
• Gliclazide MR had a better safety profile than
  glimepiride.

32
INSULINE SECRETAGOGUES-Ia

• Nateglinide metformin vs gliclazide metformin
• No significant difference was seen between the
  groups in terms of HbA1c
• Glimepiride metformin vs glimepiride vs
  metformin
• Combination treatment was more effective than
  either drug alone in terms of glycaemic control.
• Combination therapy was more effective than
  either drug in reducing TC levels.

33
ACARBOSE-Ia

• Failed to demonstrate better glycaemic control
  when compared with other oral agents.
• It did not demonstrate superiority over other
  oral agents when lipid profile and body weight
  were evaluated.
• Reports of adverse effects were higher with
  acarbose. (GI complaints Flatulence).

34
GLITAZONES pioglitazone and rosiglitazone-Ia

• Alternative to treatment with a combination of
  metformin and a sulfonylurea is not recommended
  except for those who are unable to take metformin
  and a sulfonylurea in combination because of
  intolerance or a contraindication to one of the
  drugs.

35
Exenatide GLP-1 mimetics Ib

• Indicated for treatment of Type 2 diabetes
  mellitus in combination with metformin and/or
  sulphonylureas in patients who have not achieved
  adequate glycaemic control on maximally tolerated
  doses of these oral therapies.
• SC. 5 mcg twice daily for one month then it can
  be increased to 10 mcg twice daily.
• 1 h before meals.

36
ADVERSE EFFECTS- Ia

• The main differences across all the different
  treatment groups were
• The high frequency of gastrointestinal (GI)
  complaints reported by metformin-treated
  patients.
• The high frequency of hypoglycaemic events
  reported by sulfonylurea-treated patients.
• The high number of episodes of oedema reported by
  glitazone-treated patients.
• The high number of cases of upper respiratory
  infection in patients treated with metiglinides.

37
Oral agents and Insulin therapy

• Patients receiving a combination treatment with
  insulin (NPH or pre-mixes) and metformin or a
  sulfonylurea showed significantly lower HbA1c
  levels when compared to those treated with
  insulin monotherapy.
• InsulinOHA combination therapy was associated
  with a significantly lower insulin dose compared
  to insulin monotherapy.
• There is no difference in Well-being, quality of
  life or treatment satisfaction.

38
INSULIN THERAPY

• Access to the types of insulin they find allow
  them optimal well-being. A
• Cultural preferences need to be discussed and
  respected. D
• Multiple insulin injection regimens, in adults
  who prefer them, should be used as part of an
  integrated package of which education, food and
  skills training should be integral parts. A

39
INSULIN THERAPY

• Meal-time insulin injections should be provided
  by injection of unmodified (soluble) insulin or
  rapid-acting insulin analogues before main meals.
  D
• Rapid-acting insulin analogues should be used as
  an
• alternative to meal-time unmodified insulin
  A
• Where nocturnal or late inter-prandial
  hypoglycaemia is a problem.
• In those in whom they allow equivalent blood
  glucose
• control without use of snacks between meals
  and this
• is needed or desired.

40
INSULIN THERAPY -D

• Basal insulin supply should be provided by the
  use of isophane (NPH) insulin or long-acting
  insulin analogues (insulin glargine).
• Isophane(NPH) insulin should be given at bedtime.
  
• If rapid-acting insulin analogues are given at
  meal times, the need to give isophane (NPH)
  insulin twice daily (or more often) should be
  considered.

41
INSULIN THERAPY-D

• Long-acting insulin analogues (insulin glargine)
  should be used when
• Nocturnal hypoglycaemia is a problem on
  isophane (NPH) insulin.
• Morning hyperglycaemia on isophane (NPH)
  insulin results in difficult daytime blood
  glucose control.
• Rapid-acting insulin analogues are used for
  meal-time blood glucose control.

42
INSULIN THERAPY-D

• Twice-daily insulin regimens should be used by
  those adults who consider number of daily
  injections an important issue in quality of life.
• Biphasic insulin preparations (pre-mixes).
• Advantage to those prone to hypoglycaemia at
  night.
• Such twice daily regimens may also help
• Those who find adherence to their agreed
  lunch-time
• insulin injection difficult.
• Adults with learning difficulties who may
  require
• assistance from others.

43
INSULIN THERAPY-D

• Adults with erratic and unpredictable blood
  glucose
• control rather than a change in a previously
  optimised insulin regimen, the following should
  be considered
• Resuspension of insulin and injection
  technique.
• Injection sites
• Self-monitoring skills.
• Knowledge and self-management skills
• Nature of lifestyle
• Psychological and psychosocial difficulties
• Possible organic causes such as gastroparesis.

44
INSULIN THERAPY-NICE

• Continuous subcutaneous insulin infusion (or
  insulin pump therapy) is recommended WHEN
• Multiple-dose insulin therapy (including, where
  appropriate, the use of insulin glargine) has
  failed.
• Those receiving the treatment have the
  commitment and competence to use the therapy
  effectively.

45
INSULIN DELIVERY-D

• Access to the insulin injection delivery device
  they find allows them optimal well-being, often
  using one or more types of insulin injection pen.
• Insulin injection should be made into the deep
  subcutaneous fat. To achieve this, needles of a
  length appropriate to the individual should be
  made available.

46
INSULIN DELIVERY-D

• Abdominal wall is the therapeutic choice for
  meal-time insulin injections.
• Isophane (NPH) insulin, may give a longer profile
  of action when injected into the subcutaneous
  tissue of the thigh rather than the arm or
  abdominal wall.
• Use one anatomical area for the injections given
  at the same time of day, but to move the precise
  injection site around in the whole of the
  available skin within that area.

47
HYPOGLYCAEMIA

• Specific education on the detection and
  management of hypoglycaemia in adults with
  problems of hypoglycaemia awareness should be
  offered. D
• Adults should be informed that late post-prandial
  hypoglycaemia may be managed by appropriate
  inter-prandial snacks or the use of rapid-acting
  insulin analogues before meals. D
• Any available glucose/sucrose-containing fluid is
  suitable for the management of hypoglycaemic
  symptoms or signs in people who are able to
  swallow. A

48
HYPOGLYCAEMIA

• Adults with decreased level of consciousness due
  to hypoglycaemia who are unable to take oral
  treatment safely should beD
• Given intramuscular glucagon by a trained user
  (intravenous glucose may be used by professionals
  skilled in obtaining intravenous access).
• Monitored for response at 10 minutes, and then
  given intravenous glucose if the level of
  consciousness is not improving significantly.
• Then given oral carbohydrate when it is safe to
  administer it, and placed under continued
  supervision.

49
HYPOGLYCAEMIA

• Review should be made of the following possibly
  contributory causes D
• Inappropriate insulin regimens (incorrect dose
  distributions and insulin types).
• Meal and activity patterns, including alcohol.
• Injection technique and skills.
• Injection site problems.
• Possible organic causes including
  gastroparesis.
• Changes in insulin sensitivity (the latter
  including drugs affecting the renin-angiotensin
  system and renal failure).
• Psychological problems.
• Previous physical activity.
• Lack of appropriate knowledge and skills for
  self
• management.

50
ARTERIAL RISK- C

• Should be assessed annually
• Albumin excretion rate.
• Smoking.
• Blood glucose control.
• Blood pressure.
• Full lipid profile (including HDL and LDL
  cholesterol and triglycerides).
• Age.
• Family history of arterial disease.
• Abdominal adiposity.

51
ARTERIAL DISEASE

• Advice on smoking cessation. D
• Aspirin therapy (75 mg daily) should be
  recommended in adults with high and
  moderately-high risk. B
• A standard dose of a statin should be recommended
  for adults in the highest risk and
  moderately-high-risk groups. Therapy should not
  be stopped if alanine aminotransferase is raised
  to less than three times the upper limit of
  reference range. B

52
BLOOD PRESSURE-D

• Blood pressure should be 135/85 mmHg unless the
  person has abnormal albumin excretion rate or
  two or more features of the metabolic syndrome ,
  in which case it should be 130/80 mmHg.

53
RETINOPATHY-A

• Eye surveillance for adults newly diagnosed with
  should be started from diagnosis.
• Structured eye surveillance should be at 1-year
  intervals.

54
NEFROPATHY

• All adults should be asked to bring in a
  first-pass morning urine specimen once a year.
  This should be sent for estimation of
  albumincreatinine ratio. Estimation of urine
  albumin concentration alone is a poor
  alternative. Serum creatinine should be measured
  at the same time. D
• ACE inhibitors should be started. A
• If ACE inhibitors are not tolerated, angiotensin
  2 receptor
• antagonists should be substituted.
  Combination therapy is
• not recommended at present. B
• The patient should be advised about the
  advantages of not following a high protein diet. B

55
FOOT CARE

• Structured foot surveillance should be at 1-year
  intervals, and should include educational
  assessment D
• Inspection and examination of feet should
  include D
• Skin condition.
• Shape and deformity.
• Shoes.
• Impaired sensory nerve function.
• Vascular supply (including peripheral pulses).
• Use of a 10 g monofilament plus non-traumatic pin
• prick is advised for detection of impairment
  of sensory nerve function. DS

56
FOOT ULCERATION RISK-D

• Low current risk (normal sensation and palpable
  pulses).
• Increased risk (impaired sensory nerve function
  or
• absent pulses, or other risk factor).
• High risk (impaired sensory nerve function and
  absent pulses or deformity or skin changes, or
  previous ulcer).
• Ulcer present.

57
NEUROPATHY

• Men should be asked annually whether erectile
  dysfunction is an issue. D
• PDE5 (phosphodiesterase-5) inhibitor drug, if not
  contraindicated, should be offered where erectile
  dysfunction is a problem. A
• In adults with diabetes on insulin therapy who
  have erratic blood glucose control or unexplained
  bloating or vomiting, the diagnosis of
  gastroparesis should be considered. D
• In this case, a trial of prokinetic drugs is
  indicated (metoclopramide or domperidone, with
  cisapride as third line if necessary). D

58
NEUROPATHY-D

• When the patient presents with unexplained
  diarrhoea, particularly at night, the possibility
  of autonomic neuropathy affecting the gut should
  be considered.
• Adults with diabetes who have bladder emptying
  problems should be investigated for the
  possibility of autonomic neuropathy affecting the
  bladder, unless other explanations are adequate.

59
DIABETES AND CARDIOVASCULAR RISK
60
DIABETES AND CARDIOVASCULAR RISK

• Nearly all people with Type 2 diabetes are at
  high cardiovascular (CV) risk.
• The excess risk is independently associated
  with
• Hyperglycaemia .
• High blood pressure (BP).
• Dyslipidaemia, typically the low high-density
  lipoprotein cholesterol (HDL-C) and raised
  triglyceride (TG) levels.

61
DIABETES AND CARDIOVASCULAR RISK

• Consider a person to be at high premature
  cardiovascular risk for his or her age unless he
  or she
• Is not overweight, tailoring this with an
  assessment of body weight associated risk
  according to ethnic group.
• Is normotensive (lt140/80 mmHg in the absence of
  antihypertensive therapy).
• Does not have microalbuminuria.
• Does not smoke.
• Does not have a high-risk lipid profile.
• Has no history of cardiovascular disease.
• Has no family history of cardiovascular disease.

62
DIABETES AND CARDIOVASCULAR RISK

• The risk of each of the microvascular and
  macrovascular complications of Type 2 diabetes is
  strongly associated with hyperglycaemia as
  measured by updated mean HbA1c.
• Cardiovascular risk can be reduced by 1015 per
  1.0 reduction of HbA1c.

63
DIABETES AND CARDIOVASCULAR RISK

• A single target figure is unhelpful as this may
  vary in individuals depending on the
• - Quality of life that might have to be
  sacrificed in reaching the target.
• - Extent of side effects.
• - Resources available for management.
• - An individual requiring insulin for adequate
  control, who is at risk and prone to
  hypoglycaemia would have a higher personal target
  of glucose control.

64
DIABETES AND CARDIOVASCULAR RISK

• When setting a target glycated haemoglobin
  HbA1c
• Involve the person in decisions about their
  individual HbA1c target level.
• Encourage the person to maintain their
  individual target unless the resulting side
  effects (including hypoglycaemia) or their
  efforts to achieve this impair their quality of
  life.
• Offer therapy (lifestyle and medication) to help
  achieve and maintain the HbA1c target level.
• Avoid pursuing highly intensive management to
  levels of less than 6.5 .

65
EVIDENCE SEARCH
66

• NICE
• National clinical guideline for management of
  type 1 diabetes and type 2 diabetes in primary
  and secondary care.
• Type 2- Diabetes- newer agents.
• Guidance for patients.
• NEW ZEALAND GUIDELINES GROUP
• Management of type 2 Diabetes.

67

• NATIONAL GUIDELINES CLEARING HOUSE
• Best practice guideline for the subcutaneous
  administration of insulin in adults with type 2
  diabetes.
• Guidelines for the practice of diabetes
  education.
• American Association of Clinical Endocrinologists
  medical guidelines for clinical practice for the
  management of diabetes mellitus. Nutrition and
  diabetes.

68

• TRIPDATABASE
• Basic guidelines for diabetes care.
• Wisconsin essential diabetes mellitus care
  guidelines.
• COCHRANE
• Exercise for type 2 diabetes mellitus.
• Group based training for self-management
  strategies in people with type 2 diabetes
  mellitus.
• Individual patient education for people with type
  2 diabetes.
• ROYAL COLLEGE OF PHYSICIANS
• Type 2 Diabetes update.
• Type 2 Diabetes footcare.

69

• MEDLINE
• Diabetes resources
• American Diabetes Association -
  www.diabetes.org
• Juvenile Diabetes Research Foundation
  International www.jdrf.org
• National Center for Chronic Disease
  Prevention and Health Promotion -
  www.cdc.gov/diabetes/
• National Diabetes Education Program -
  http//ndep.nih.gov/
• National Diabetes Information Clearinghouse -
  www.diabetes.niddk.nih.gov
• FISTERRA
• Diagnose and management algorythm.

70
Thank you !!
71
Anexus 1 Sulfonylureas

• They act by increasing insulin release from the
  beta cells in the pancreas.
• First generation
• Acetohexamide
• Chlorpropamide
• Tolbutamide
• Tolazamide
• Second generation
• Glipizide
• Gliclazide
• Glibenclamide (glyburide)
• Gliquidone
• Glyclopyramide
• Third generation
• Glimepiride