P3. p 135 - 158

Question 1

In terms of diabetes in the USA:

1) What is the overall prevalence of diabetes & prediabetes (2015) ?
2) What ethnic groups have an increased/decreased risk
3) In children born after 2000, approx what proportion will develop NIDDM
4) What are the medical costs compared to those without diabetes ?

BR 146

Answer 1

1) Diabetes prevalence 9.3%, prediabetes ~ 33% (84 million) => 10% & 30%
2) Increased in American Indian (15%), blacks (12.7%), Hispanics (12.1%). Less in Asian (8%), whites (7.4%).
3) Born after 2000 risk of diabetes is 33% in males, 39% in females and 50% in Blacks/Hispanics

=> 30% males, 40% females, 50% black/Hispanic

4) Medical costs are 2.3 X higher (vs non-diabetics) and average $ 16,750/yr of which $ 9,600 is attributed to diabetes.

Question 2

In terms of global rates of NIDDM

1) What were the global rates in 1980 and 2014 ?
2) What is the anticipated global increase by 2025 ?
3) In India, how many people have diabetes and what are the cost implications ?

BR 147

Answer 2

1) Global rate went from ~ 5% to 8.5% from 1980 to 2014
2) By 2025 anticipated global increase is 55%
3) In India currently, 100 million have diabetes; when present the cost of care consumes about 25% of the family’s income.

Question 3

In the ACCORD trial

Describe the:
Aim, population, intervention, outcomes

List 3 outcomes/complications of study

NEJM 2008:358(24):254

Answer 3

Aim: whether intensive therapy to target normal glycated hemoglobin levels would reduce cardiovascular events in patients with type 2 diabetes who had either established cardiovascular disease or additional cardiovascular risk factor

Population: 10,251 pts with median HbA1c of 8.1%

Interventions:

Intensive Rx to get HbA1c below 6.0% vs standard therapy with target HbA1c of 7.0-7.9%

Primary outcome: Composite vascular: of nonfatal MI, nonfatal CVA or death from CV causes

Results:

1) At 1 yr median HbA1c acheived was 6.4% vs 7.1%
2) At 3.5 yrs HR of primary outcome was 0.90 (P=NS) however mortality HR was 1.22 (P=0.04)

=> primary -10%, mortality + 20%

3) Hypoglycemia requiring assistance and weight gain of > 10 kg were more common in the intensive therapy group.

ACCORD: Action to COntrol CV Risk in Diabetes

Question 4

What is meant by ‘reversal of type 2 diabetes’ ?

BR 148

Answer 4

Reversal of NIDDM:

1) Normalization of blood sugar and HbA1c
2) Discontinuation of all diabetes medications (oral & injectable).

Question 5

What is the role of leptin in NIDDM ?

BR 149

Answer 5

• leptin is produced by adipocytes
• Leptin resistance results in the inability to detect satiety signals which further drives the sensation of hunger => consume more calories.
• Leptin is also pro-angiogenic meaning it triggers new blood vessel growth which can increase the risk of cancer cell growth and metastases.

Question 6

What is the possible role of heme iron in NIDDM

BR 150

Answer 6

• Heme iron & diets high in red and processed meat are associated with an increased risk of NIDDM & insulin resistance.
• Heme iron stores are pro-oxidants.

Question 7

What is the role of beta cells and associated factors in NIDDM ?

List factors which can contribute to beta cell death

BR 150

Answer 7

• beta cells in the pancreas produce insulin.
• beta cell death can be due to:
  1) Hyperlipidemia - VLDL & LDL are pro-apoptotic
  2) Hyperglycemia
  3) Cytokines: NF kappa B, JNK pathways
  4) Leptin => stimulates cytokine pathways => apoptosis
  5) Oxidative stress and free fatty acids (via NF kappa B & JNK pathways).

Question 8

Name 5 ways in which a Whole Food Plant-based diet protects beta cells.

BR 158

Answer 8

S - Stabilises immune System via multiple pathways

H - Hyperglycemia avoided - protects against apoptosis

I - Inflammatory pathways downregulated

L - Lipid profile normalised

L - Leptin/adiponectin pathway normalised

Mnemonic - ‘SHILL’.