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What Is New In Diabetes: An Update. David W. Gardner MD Director Cosmopolitan International Diabetes Center University of Missouri School of Medicine Columbia, MO . What’s New and Important. How to diagnose diabetes Identifying and treating prediabetes Unusual forms of diabetes

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what is new in diabetes an update

What Is New In Diabetes: An Update

David W. Gardner MD

Director

Cosmopolitan International Diabetes Center

University of Missouri School of Medicine Columbia, MO

what s new and important
What’s New and Important
  • How to diagnose diabetes
  • Identifying and treating prediabetes
  • Unusual forms of diabetes
  • What should glycemic goals be?
  • New and possible future treatments of diabetes
  • Obesity and diabetes
slide4
Guidelines and Recommendations for Laboratory Analysis in the Diagnosis and Management of Diabetes Mellitus

Any one of the following is diagnostic:

1. HbA1c >6.5% (48 mmol/mol)

OR

2. FPG > 7.0 mmol/L (126 mg/dL)

OR

3. 2-h Plasma glucose > 11.1 mmol/L (200 mg/dL) during an OGTT

OR

4. Symptoms of hyperglycemia and casual plasma glucose > 11.1 mmol/L (200 mg/dL)

Diabetes Care 34:e61–e99, 2011

recommendation of the international expert committee for the diagnosis of diabetes
Recommendation of the International Expert Committee for the Diagnosis of Diabetes

A1c > 6.5% = Diabetes

Levels at which the Dx is made based on when the risk for retinopathy goes up

cvd is the leading cause of mortality in patients with diabetes
CVD is the Leading Cause of Mortality in Patients With Diabetes

The CV Risk Increases Dramatically When A1c is Between 5 and 6%

  • Followed 4662 men and 5570 women who were 45 to 79 for 6-8 years
  • Checked baseline A1c and risk factors
  • Followed until 2003 for CVD events and mortality
  • Relationship between A1c and CVD and all-cause mortality was continuos
    • With out known DM
  • Increase of 1% associated with mortality RR of 1.24 in men

RR Coronary Heart

Disease Event

A1c

Ann Intern Med. 2004;141:413-420.

prevalence of diabetes and high risk for diabetes using a1c criteria in the u s
Prevalence of Diabetes and High Risk forDiabetes Using A1C Criteria in the U.S
  • Used NHANES data to look of incidence of DM (diagnosed and undiagnosed) and at risk for diabetes (IFG, IGT, Prediabetes)
  • Conclusion: Using the A1c criteria, there is a much lower prevalence of DM and Prediabetes than glucose criteria

Diabetes Care 33:562–568, 2011

prevalence of diabetes and high risk for diabetes using a1c criteria in the u s8
Prevalence of Diabetes and High Risk forDiabetes Using A1C Criteria in the U.S

Diabetes Care 33:562–568, 2011

performance of glycated hemoglobin for the classification and prediction of diabetes
Performance of Glycated Hemoglobin for the Classification and Prediction of Diabetes
  • Objective: “assess the test performance of HbA1c against single and repeat glucose measurements for diagnosis of prevalent diabetes and for prediction of incident diabetes”
  • It was a Population-based analyses of 12,485 participants
  • Compared to a single fasting glucose the A1c had:
    • a sensitivity of 47% and
    • specificity (Sp) of 98%
  • An HbA1c cut-point of 6.5% is highly specific but has low sensitivity for the identification of prevalent undiagnosed diabetes

Diabetes Care Publish Ahead of Print, published online September 20, 2010

what should we do
What Should We do?
  • 2 hr PP glucose has the highest specificity
    • Hard to do in office practice
  • FPG is better than A1c as single test
  • A1c is easy to do and has a high specificity
    • More expensive
    • Effected by hemoglobinopathies, hemolysis and anemia
my suggestion
My Suggestion

Screen with FPG and A1c

  • If FPG < 100 mg/dl and A1c <6.0%: Normal glucose tolerance
  • If FPG > 126 and A1c> 6.5%: Dx diabetes
  • If one is diagnostic of DM and other is not: repeat the high test and if still positive: Dx diabetes
  • If one or both in Prediabetic (FPG >100 and <126 mg/dl) or At risk range (A1c >6.0 and <6.5), do a 2hr PP glucose after 75 gm of glucose
    • If >200 mg/dl repeat to confirm Dx DM
    • If >140 and <200 mg/dl Dx with IGT, prediabetes or at risk for diabetes
    • Follow carefully
prediabetes

Prediabetes

Impaired Glucose Tolerance (IGT), Impaired Fasting Glucose (IFG), At risk for diabetes

previous criteria
Previous Criteria

IFG

IGT

New Guidelines 6.0-6.5% should be considered at “Higher Risk for Diabetes”

diabetes prevention program dpp
Diabetes Prevention Program (DPP)

Randomized 3234 subject with impaired glucose tolerance (prediabetes) to

Intensive lifestyle intervention or

Metformin and usual lifestyle intervention or

Placebo and usual lifestyle

Endpoint: development of diabetes mellitus

Goal of intensive lifestyle intervention was

7% reduction in body weight and

150 minutes of physical activity a week

NEJM 2002 346:393-403

diabetes prevention program dpp15
Diabetes Prevention Program (DPP)

Intensive lifestyle intervention:

One on one weekly instruction for 16 weeks

Individualized diet and exercise program designed for each subject

Monthly contact with a specially trained instructor for review of diet and exercise after initial 16 weeks

Provide exercise facilities 3 times/week

If not meeting goal, revising of the program to meet the individual needs of the subject

NEJM 2002 346:393-403

diabetes prevention program dpp16
Diabetes Prevention Program (DPP)

In the intensive lifestyle intervention group

74% met the goal of 150 minutes of physical activity per week at 24 weeks

Daily energy intake decreased by 450 kcal

Only fifty percent of the participants in the lifestyle intervention group had achieved the goal of weight loss of 7% or more by the end of 24 weeks

38 percent had a weight loss of at least 7% at the time of the most recent visit

NEJM 2002 346:393-403

diabetes prevention program dpp18
Diabetes Prevention Program (DPP)

The intensive lifestyle intervention group had a 58% reduction in the risk of developing diabetes

Metformin had a 31% decrease in risk of DM

With

Extensive education and resources devoted to education

74% maintaining 150 minutes of activity/week and

Average decreased intake of 450 kcal/day

Maximal weight loss was achieved at 6 months

Average maximal weight loss was 13 lbs. (6.3%)

Weight steadily increased for the remainder of the study

NEJM 2002 346:393-403

diabetes prevention program dpp19
Diabetes Prevention Program (DPP)

Sub Group Analysis

In women with a history of Gestational DM Metformin and lifestyle intervention were similarly effective

In older subjects (>60 years of age at baseline), the lifestyle intervention was particularly effective (72 percent reduction in diabetes compared with placebo),

Metformin was relatively less effective.

In younger subjects with BMIs > 35 metformin was as effective as intensive lifestyle intervention

NEJM 2002 346:393-403

dpp 10 year followup weight change
DPP 10 Year Followup: Weight Change

4 lbs

5

10

Years Since Randomization

Lancet 2009; 374: 1677–86

dpp 10 year followup incidence of dm
DPP 10 Year Followup: Incidence of DM

10

5

Years Since Randomization

Lancet 2009; 374: 1677–86

prediabetes igt ifg at risk for diabetes
Prediabetes (IGT, IFG, “At Risk For Diabetes”)
  • First have to diagnose it
    • Greatly underdiagnosed
    • Screen high risk individuals
    • Screen with FPG and A1c
  • Intensive life style intervention was very intensive
    • Sending to dietician and giving a book on exercise is not enough!
    • Likely to be expensive
  • If aggressive lifestyle not feasible or BMI > 35, Metformin is just as effective
secondary types of dm

Secondary Types of DM

Neither Type 1 or 2 DM

secondary diabetes
Secondary Diabetes
  • Diseases of the Exocrine Pancreas
    • Pancreatitis/pancreatectomy
    • Neoplasia
    • Cystic fibrosis
    • Hemochromatosis
  • Endocrinopathies
    • Acromegaly
    • Cushing syndrome
    • Glucagonoma
    • Pheochromocytoma
    • Hyperthyroidism
    • Somatostatinoma
    • Aldosteronoma
  • Infections
    • Congenital rubella
    • Cytomegalovirus
secondary diabetes25
Secondary Diabetes
  • Drug- or Chemical-induced
  • Genetic Defects in Insulin Action
    • Type A insulin resistance
    • Leprechaunism
    • Rabson-Mendenhall syndrome
    • Lipoatrophic diabetes
  • Other Immune-Mediated Diabetes
    • Stiff man syndrome etc
    • Anti-insulin receptor antibodies
  • Other Genetic Syndromes
    • Down syndrome, Klinefelter syndrome, Turner syndrome, Wolfram syndrome, Friedreich ataxia, Huntington chorea, Laurence-Moon-Biedl syndrome, Myotonic dystrophy, Porphyria Prader-Willi syndrome
secondary diabetes26
Secondary Diabetes
  • Genetic Defects of ß-cell Function
    • Neonatal diabetes
    • Maturity-onset Diabetes of Youth (MODY)
      • MODY 1 - Chromosome 20, hepatocyte nuclear factor (HNF) -4α
      • MODY-2 Chromosome 7, glucokinase
      • MODY3 - Chromosome 12, HNF-1α
      • MODY4- Chromosome 13, insulin promoter factor-1 (IPF-1)
      • MODY5- Chromosome 17, HNF-1ß
      • MODY6 - Chromosome 2, neurogenic differentiation 1
    • Mitochondrial DNA
slide27
MODY
  • Heterogeneous group of monogenetic defects that usually limit the ability of the beta cell to produce insulin
  • Often diagnosed in adolescence
    • Very strong family history (Autosomal Dominant)
    • Often not obese and no ketones
  • Accounts for 1-5% of diabetes
  • Often do well with sulfourea monotherapy
  • Genetic testing can identify them
  • Importance:
    • 1-5% of patients can be treated with SU
    • Young adults might be Dx type 1 by mistake
    • Family screen can be done and Dx earlier
latent autoimmune diabetes of adults lada29
Latent Autoimmune Diabetes of Adults (LADA)
  • Different Names:
    • LADA
    • “Type 1.5 Diabetes,”
    • “Antibody-Positive Type 2 Diabetes,”
    • “Latent Type 1 Diabetes,”
    • “Double Diabetes,” and
    • “Youth Overt Diabetes of Maturity (YODM).”
  • LADA may comprise up to 10-15% of adults diagnosed with Type 2 diabetes.
    • Initially, it presents phenotypically as Type 2,
    • Autoimmune markers for Type 1 DM, such as anti-GAD antibodies, are present.
latent autoimmune diabetes of adults lada30
Latent Autoimmune Diabetes of Adults (LADA)
  • LADA is generally considered to be a slowly progressive form of Type 1 diabetes
  • LADA patients do not require insulin early in the coarse of DM
  • Oral agents work initially but generally fairly early
    • Particularly sulfonylureas
keys to recognize lada
Keys to Recognize LADA
  • Negative family history for Type 2 DM
  • Positive family history for Type 1 DM
  • Non obese
  • Ketones in urine
  • Early failure of oral agents
    • Most type 2 patients do well on oral agents for several years

Diagnosis

  • Measure GAD-65 anybody
    • Positive very likely LADA
  • Simultaneous glucose and C-Peptide or post meal C-Peptide
    • No national criteria for what is diagnostic values
treatment of lada
Treatment of LADA
  • If glycemic control is at goal on oral agents, continue them
  • Watch closely for worsening control on oral agents
    • If 2 agents are failing (A1c>7.0%) change to insulin
      • May continue metformin
    • Usually need to go to basal/bolus
  • If ketones persistently positive start insulin
  • Recognition is important so insulin treatment is not delayed as A1c climbs
glycemic goals

Glycemic Goals

What should the A1c goal be?

ukpds results of intensive therapy with sulfonylurea insulin
UKPDS: Results of Intensive Therapy With Sulfonylurea/Insulin

P*= 0.029

0.0099

0.015

0.000054

0.052

*Difference in median HbA1c was 0.9%

Lancet 352:837-853 1998

a1c 10 years after end of ukpds
A1c 10 Years After End of UKPDS

Differences In Glycemic Control Lost in 1 year

NEJM Published on line 9/10/08

mortality 10 years after end of ukpds
Mortality 10 Years After End of UKPDS

Conventional Rx: SU & Insulin

Conventional Rx: Metformin

NEJM Published on line 9/10/08

ukpds 10 year observation
UKPDS 10 year Observation

Differences In glycemic control were lost early

In the Sulfonylurea Insulin group,

Benefits of better glycemic control emerged for myocardial infarction, and overall survival

All diabetic endpoints and microvascular outcomes continue to be significant

In the metformin treated group

Continued benefit in myocardial infarction, mortality, and all diabetic end points continued

NEJM Published on line 9/10/08

metaanalysis of effects of glycemic control cardiac events and all cause mortality
Metaanalysis of effects of Glycemic control, Cardiac events and all cause mortality
  • Published in Lancet may of 2009
  • Looked at ACORD, ADVANCE, VADT, and added UKPDS (original results) and PROactive
  • The total numbers of events in each group was significantly less than predicted and this decreased the chance of finding a positive result
    • By combining the trials there were enough events to answer the question
  • In the metaanalysis the combined difference in A1c was 0.9%

Lancet 2009; 373: 1765–72

probability of non fatal myocardial infarction intensive glucose lowering a1c 6 6 vs 7 5
Probability of Non-Fatal Myocardial Infarction Intensive Glucose lowering A1c 6.6% vs 7.5%

A1c 6.6

A1c 7.5

Lancet 2009; 373: 1765–72

slide41

Aggressive Therapy of DM Saves Lives, Decrease Traditional Microvascular Complications and Decreases MIs!!!!

The Benefit Persists Years After Control Gets Worse

the year of hypoglycemia
The Year of Hypoglycemia!
  • Recent trials have emphasized the risk of hypoglycemia
  • The adverse effects may not be seen at the time the glucose is low but rather effects long term outcomes
hypoglycemic episodes and risk of dementia in older patients with type 2 diabetes mellitus
Hypoglycemic Episodes and Risk of Dementia in Older Patients With Type 2 Diabetes Mellitus
  • Longitudinal cohort study of 16,667 patients with type 2 DM
  • Mean age of 65 years
  • Looked at severe hypoglycemia requiring ED visit or hospitalization
  • Compared with patients with no hypoglycemia, patients with single or multiple episodes had a graded increase in risk for dementia
    • 1 episode HR, 1.26;
    • 2 episodes HR, 1.80;
    • 3 or more episodes HR, 1.94;

JAMA. 2009;301(15):1565-1572 www.jama

hypoglycemia and clinical outcomes in patients with diabetes hospitalized in the general ward
Hypoglycemia and Clinical Outcomes in Patients With Diabetes Hospitalized in the General Ward
  • This retrospective cohort study analyzed 4,368 admissions of 2,582 patients with diabetes
  • Looked at the associations between the number and severity of hypoglycemic (50 mg/dl) episodes and inpatient mortality, length of stay (LOS), and mortality within 1 year after discharge were evaluated

Diabetes Care 32:1153–1157, 2009

hypoglycemia and clinical outcomes in patients with diabetes hospitalized in the general ward46
Hypoglycemia and Clinical Outcomes in Patients With Diabetes Hospitalized in the General Ward

Risk of 1 year mortality

Increase in length of Stay

Diabetes Care 32:1153–1157, 2009

aggressive glycemic control a two edged sword
Aggressive glycemic control: A two edged sword!
  • Lower glucose levels associated with improved outcomes
  • The lower the glucose levels and A1c, the greater the risk of hypoglycemia
    • 1% decrease in A1c results in a 3 fold increase in severe hypoglycemia
    • This is with agents that can cause hypoglycemia (insulin and sulfonylureas)
  • Increased hypoglycemia associated with increases in adverse outcomes
goals for glycemic control
Goals For Glycemic Control
  • AACE, A1c < 6.5%
  • ADA and EASD A1c <7%
    • If you can achieve lower A1c with increased risk of hypoglycemia or other adverse events, it should be considered
  • Important caveats:
    • Goals are patient directed
      • Benefit should outweigh risk in a given patient
    • Establish good control as early as possible and for as long as possible in DM
    • To avoid hypoglycemia with aggressive control, choose agents that have a low risk of hypoglycemia
therapeutic options
Therapeutic options
  • Metformin Hypoglycemia NO
  • Sulfonylureas Hypoglycemia YES
  • Insulin Hypoglycemia YES
  • TZD (Actos, etc) Hypoglycemia NO
  • Incretins Hypoglycemia NO
  • Bile acid sequestrant Hypoglycemia NO
  • Bromocriptine (Cycloset) Hypoglycemia NO
  • Bariatric surgery Hypoglycemia Possible

Only 2 classes of agents cause hypoglycemia when used alone!

what is the role of glucagon

What is the role of glucagon?

Late breaking results!

the pathogenesis of type 2 diabetes beta cell workload outpaces beta cell response
The Pathogenesis of Type 2 DiabetesBeta-Cell Workload Outpaces Beta-Cell Response

Defects in Insulin and Glucagon in Type 2 Diabetes

Healthy Subjects (n = 14)

Type 2 Diabetes (n = 12)

Carbohydrate Meal

N Engl J Med 1970;283:109-115

post prandial abnormalities not corrected by i v insulin
Post Prandial Abnormalities Not Corrected by I.V. Insulin

Unger RH:. NEngl J Med 285:443–449, 1971

the incretin effect beta cell response to oral vs iv glucose
The Incretin Effect Beta-Cell Response to Oral vs IV Glucose

*

*

*

*

Incretin Effect

*

*

Type 2 DM

*

Incretin Effect:

Better insulin Response to Oral Than IV Glucose

J Endo Metab 1986;63:492-498

incretins59
Incretins

1. Glucagon-Like Peptide 1 (GLP)

2. Glucose Dependent Insulinotropic

Polypeptide (GIP)

These two account for 90% of

the incretin effect

leveraging the therapeutic potential of glp 1
Leveraging the Therapeutic Potential of GLP-1

Incretin mimetics

Mimic benefits of GLP-1

But are resistant to degradation by DPP-IV

DPP-IV inhibition

Extends endogenous GLP-1 half-life

Approaches to this problem

dpp iv inhibitors

DPP IV Inhibitors

Three have been approved so far

dpp4 inhibitors
DPP4 Inhibitors
  • About 0.7% reduction in A1c
  • Once daily
  • No weight gain
  • Low risk of hypoglycemia
  • No titration
  • Low side effect profile
    • Allergic reaction
    • Possible increased risk of pancreatitis
  • Easy to use in office
exenatide byetta is a glp 1 mimetic
Exenatide (Byetta) is a GLP-1 Mimetic
  • Like GLP-1 but not effected by DPP-IV
  • Twice daily injection
  • 0.7-1.0 reduction in A1c
  • No hypoglycemia
  • Weight neutral to weight loss
    • Can be substantial
  • Requires training in injection (has pen) and titrations
  • Side effects
    • GI with nausea and vomiting
    • Possible increase risk of pancreatitis
exenatide once weekly bydureon
Exenatide Once-weekly (Bydureon)
  • Not yet approved by FDA
  • Once weekly injection with special device
  • Very long acting preparation
  • A1c reduction 1.3-1.5%
  • Currently investigating once monthly injection
    • Looks promising
duration 5 exenatide once weekly
DURATION-5: Exenatide Once Weekly

Exenatide Twice Daily

Exenatide Once Weekly

The Journal of Clinical Endocrinology & Metabolism

Issue: Volume 96(5), May 2011, p 1301–1310

duration 5 exenatide once weekly70
DURATION-5: Exenatide Once Weekly

Exenatide Twice Daily

Body Wt

Exenatide Once Weekly

The Journal of Clinical Endocrinology & Metabolism

Issue: Volume 96(5), May 2011, p 1301–1310

liraglutide victoza
Liraglutide (Victoza)
  • GLP-1 analog
  • Once daily injection
    • Titrate from 0.6 mg to 1.8 mg daily
  • A1c reduction 1.1 to 1.5%
  • No hypoglycemia
  • Weight neutral to weight loss
    • Can be substantial
  • Requires training in injection (has pen) and titrations
  • Side effects
    • GI with nausea and vomiting
    • Possible increase risk of pancreatitis
slide72

June 24, 2011 — The US Food and Drug Administration (FDA) today warned healthcare professionals to closely monitor patients with diabetes receiving liraglutide injections (Victoza, Novo Nordisk) for thyroid C-cell tumors and acute pancreatitis.

liraglutide vs glimepiride
Liraglutide Vs Glimepiride

Lancet Volume 373, Issue 9662, 7-13 February 2009, Pages 473-481

liraglutide and weight loss
Liraglutide and Weight Loss

Lancet Volume 374, Issue 9701, 7-13 November 2009, Pages 1606-1616

liraglutide as additional treatment for type 1 diabetes
Liraglutide as additional treatment for type 1 diabetes.
  • 14 patients with well-controlled type 1 diabetes on continuous glucose monitoring and intensive insulin therapy were treated with liraglutide for 1 week.
    • eight continued therapy for 24 weeks.
  • Glucose levels and excursions improved
  • HbA1c decreased significantly at 24 weeks from 6.5 to 6.1% (P=0.02), as did the body weight by 4.5±1.5  kg (P=0.02).

Eur J Endocrinol. 2011 Jul;165(1):77-84. Epub 2011 Jun 6.

therapeutic options76
Therapeutic options
  • Metformin Hypoglycemia NO
  • Sulfonylureas Hypoglycemia YES
  • Insulin Hypoglycemia YES
  • TZD (Actos, etc) Hypoglycemia NO
  • Incretins Hypoglycemia NO
  • Bile acid sequestrant Hypoglycemia NO
  • Bromocriptine (Cycloset) Hypoglycemia NO
  • Bariatric surgery Hypoglycemia Possible
impact of type of preadmission sulfonylureas on mortality
Impact of Type of Preadmission Sulfonylureas onMortality

Reasons to Say Goodbye to Glyburide!

Glyburide

J Clin Endocrinol Metab 95: 4993–5002, 2010 &

Editorial J Clin Endocrinol Metab, November 2010, 95(11):4867–4870

therapeutic options78
Therapeutic options
  • Metformin Hypoglycemia NO
  • Sulfonylureas Hypoglycemia YES
  • Insulin Hypoglycemia YES
  • TZD (Actos, etc) Hypoglycemia NO
  • Incretins Hypoglycemia NO
  • Bile acid sequestrant Hypoglycemia NO
  • Bromocriptine (Cycloset) Hypoglycemia NO
  • Bariatric surgery Hypoglycemia Possible
role of tzds
Role of TZDs
  • Lower A1c
  • Delay onset of DM
  • Little or no decrease in CAD events
  • Adverse effect
    • Weight gain
    • Edema
    • Heart failure
    • Decrease in bone density and increased Fractures
    • Macular edema after one year on Rx (ADA June 2011: abstract 135-OR)
      • On TZD: 1.3%
      • No TZD: 0.2%
      • (OR 5.78, 95%CI 4.1-7.9%)
therapeutic options80
Therapeutic options
  • Metformin Hypoglycemia NO
  • Sulfonylureas Hypoglycemia YES
  • Insulin Hypoglycemia YES
  • TZD (Actos, etc) Hypoglycemia NO
  • Incretins Hypoglycemia NO
  • Bile acid sequestrant Hypoglycemia NO
  • Bromocriptine (Cycloset) Hypoglycemia NO
  • Bariatric surgery Hypoglycemia Possible
metformin
Metformin
  • Increasing evidence for low CAD events than Sulfonylurea treatment
  • FDA has approved it for use in patients with stable CHF
  • Controversy about need to decrease dose with moderate renal failure
    • FDA has not changed the contraindication for use with elevated creatinine
therapeutic options82
Therapeutic options
  • Metformin Hypoglycemia NO
  • Sulfonylureas Hypoglycemia YES
  • Insulin Hypoglycemia YES
  • TZD (Actos, etc) Hypoglycemia NO
  • Incretins Hypoglycemia NO
  • Bile acid sequestrant Hypoglycemia NO
  • Bromocriptine (Cycloset) Hypoglycemia NO
  • Bariatric surgery Hypoglycemia Possible
bile acid sequestrant
Bile acid sequestrant
  • Bile acid sequestrants low A1c about 0.5%
    • Mechanisms are not known
  • Colesevelam (WelChol) is approved to treating DM
    • Only medication approved for lowering cholesterol and a1c
  • Must be careful about interfering with absorption of many other medications
    • Take other meds one hour before or four hours after taking colesevelam
therapeutic options84
Therapeutic options
  • Metformin Hypoglycemia NO
  • Sulfonylureas Hypoglycemia YES
  • Insulin Hypoglycemia YES
  • TZD (Actos, etc) Hypoglycemia NO
  • Incretins Hypoglycemia NO
  • Bile acid sequestrant Hypoglycemia NO
  • Bromocriptine (Cycloset) Hypoglycemia NO
  • Bariatric surgery Hypoglycemia Possible
bromocriptine cycloset
Bromocriptine (Cycloset)
  • Cyclical changes in dopamine effect storage or burning of energy stored in Fat in migratory animal
  • Bromocriptine (Cycloset) is taken 2 hours after awakening with food
    • Dose is titrated weekly
    • Start at 0.8 mg and to 1.6-4.8 as tolerated
  • Associated with
    • Nausea
    • Orthostatic hypotension
type 1 dm insulin pumps
Type 1 DM: Insulin Pumps

Modern Pump

First Insulin Pump

type 1 dm glucose sensor
Type 1 DM: Glucose Sensor

Reduction in A1c with CGM

artificial pancrease
Artificial Pancrease
  • Combine Sensor and Pump with Computer
  • At present time there are Type 1 patients wearing prototypes of these units
  • Results are encouraging but much is left to be done
the realities of diet and exercise
The Realities of Diet and Exercise

Maximal achievable weight loss with current diet and medications is 10%

A consistent finding but not universal for individual patients

Virtually all of that is achieved in the first 6 months

After 6 months the same effort can only maintain the weight loss

Maintaining this is difficult

Exercise plays important role (>60 min/day)

As the patient approaches these limits, physiological mechanisms come into play that effectively block further weight loss and attempt to bring about the restoration of lost fat mass

effective obesity treatments
“Effective Obesity Treatments”

Meta analysis of long term trials of obesity treatment

Had to be randomized trial

Change in weight had to primary or secondary end point

Followup of two years or more

Trails were grouped by intervention

Lifestyle, medication, surgery

At last followup, weight loss ranged between 0.7 and 12.1 lbs compared to placebo

Difference in Wt (lbs.)

at end of each trial

April 2007 ● American Psychologist Vol. 62, No. 3, 234–246

primary care referral to a commercial provider for weight loss treatment versus standard care
Primary care referral to a commercial provider for weight loss treatment versus standard care

Standard office Care

Commercial Provider (Weight Watchers)

Lancet: Published Online September 8, 2011

primary care referral to a commercial provider for weight loss treatment versus standard care94
Primary care referral to a commercial provider for weight loss treatment versus standard care

Proportion of participants who lost at least 5% and at least 10% of their initial weight at the 12-month assessment

Lancet: Published Online September 8, 2011

surgical treatment of diabetes

Surgical Treatment of Diabetes

Bariatric surgery = Metabolic surgery

meta analysis of bariatric surgery
Meta-analysis of Bariatric Surgery
  • Diabetes resolved in 76.8%
    • Resolved or improved in 86%
  • Lipids improved in 70%
  • Hypertension resolved in 61.7%
    • Resolved or improved in 78.5%
  • Obstructive sleep apnea resolved in 85.7%
    • Resolved or improved in 83.6%

“Effective weight loss was achieved in morbidly obese patients after undergoing bariatric surgery. A substantial majority of patients with diabetes, hyperlipidemia, hypertension, and obstructive sleep apnea experienced complete resolution or improvement.”

JAMA. 2004;292:1724-1737

effects of bariatric surgery on mortality in swedish obese subjects
Effects of Bariatric Surgery on Mortality in Swedish Obese Subjects
  • A prospective, controlled study of 4047 obese subjects
    • 2010 had bariatric surgery
    • 2037 had conventional treatment
    • Looked at mortality during an average of 10.9 years
    • 99.9% follow-up rate
  • Subjects (surgery and controls) had to have BMI >34 for men and >38 for women
    • BMI at witch mortality doubles

N Engl J Med 2007;357:741-52.

long term effects of bariatric surgery
Long Term Effects of Bariatric Surgery

N Engl J Med 2007;357:741-52.

sos effects of bariatric surgery on mortality
SOS: Effects of Bariatric Surgery on Mortality

}

-24%

(Adjusted

-29%)

N Engl J Med 2007;357:741-52.

long term mortality after gastric bypass surgery
Long Term Mortality after Gastric Bypass Surgery
  • A retrospective cohort study
    • Long-term mortality from 1984-2002
    • 9949 patient post gastric bypass surgery
    • Compared 9628 severely obese who applied for driver licenses
  • They determined rates of death from any cause and from specific causes
  • During 7.1 years of followup, the adjusted long-term mortality from any cause in surgery Group was decreased by 40%!

N Engl J Med 2007;357:753-61.

long term mortality after gastric bypass surgery reduction in mortality by cause of death
Long Term Mortality after Gastric Bypass Surgery: Reduction in Mortality By Cause of Death

N Engl J Med 2007;357:753-61.

remission of diabetes
Remission of Diabetes
  • Most effective is biliopancreatic diversion/duodenal switch (95% remission
  • Lowest after laparoscopic adjustable gastric banding (57 percent)
  • Gastric Bypass is in between

JAMA. 2008;299(3):316

adjustable gastric banding and conventional therapy for type 2 diabetes
Adjustable gastric banding and conventional therapy for type 2 diabetes
  • Randomized trial in obese recently dx diabetic patients
    • BMI >30 and <40
  • Intervention:
    • Convention DM Rx and emphasis on weight loss vs.
    • laparoscopic adjustable gastric banding with conventional diabetes care
    • Followed two years
  • Results remission of DM:
    • Convention treatment: 13%
    • Surgical group: 73%
  • Remission related to weight loss

Dixon, J. B. et al. JAMA 2008;299:316-323

slide104

Percentage of Weight Loss Achieved Over the 2-Year Study Period

Dixon, J. B. et al. JAMA 2008;299:316-323

why does the diabetes get better so fast
Why does the diabetes get better so fast?
  • After gastric bypass surgery diabetes dramatically improves before there is significant weight loss
  • DM will go into remission in about 70%
  • The mechanism appear to be hormonal changes
    • GLP-1 dramatically increases
    • Ghrelin goes down and does not rise between meals
      • Ghrelin stimulate hunger in response to not eating
    • PYY increases
      • PYY is a satiety hormone in the gut
short and long term problems
Short and Long-Term Problems
  • Surgical complications are higher because of obesity
    • Leaks
    • Clots
    • Strokes
    • Population already at risk for 2 and 3
  • Hypoglycemia
    • During the OGTT Hypoglycemia in 0.9% patients before surgery, but increased significantly after surgery to 18.7%. (EASA Sept 2011, ab 60-OR)
short and long term problems108
Short and Long-Term Problems
  • Nutritional:
    • Iron deficiency
    • B12, Vitamin D deficiency and thiamine
    • Copper deficiency
metabolic surgery
Metabolic Surgery
  • Currently only successful treatment for morbid obesity
  • Treatment of diabetes mellitus
    • 50-90% remission
    • Most or improved
  • Improved: BP, Lipids, Sleep apnea
  • Decreased mortality
  • Significant complications
    • Benefit exceeds risk in these high risk patients
  • Cost effectiveness analyses vary
important areas not covered
Important Areas Not Covered
  • Inpatient glycemic control
  • Several new medications under development
  • New longer (basal) and faster (bolus) acting insulin being studied
  • Immune therapy of Type 1 Diabetes
  • Development in lipid and hypertension management
our understanding and management of dm continues to improve and change is rapid

Our understanding and management of DM Continues to improve and change is Rapid

Hopefully this will result in improved outcomes for our patients

what is new in diabetes an update112

What Is New In Diabetes: An Update

David W. Gardner MD

Director

Cosmopolitan International Diabetes Center

University of Missouri School of Medicine Columbia, MO