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GETTING IT RIGHT FROM DAY ONEMetabolic Memory and Tracking
Dr Joe Delaney PhD CSci FIBMS PhySoc
Session Outline• Individualising treatment: A Holistic Approach• Metabolic Memory and The Legacy Effect• The Evidence• Tracking – what, how and how often?• When is Day 1? • Let’s start at the very beginning...• Beyond genetics• Future directions
Type 1
Type 2 diabetes across generations: from pathophysiology to prevention and managementChristopher J Nolan, Peter Damm, Marc Prentki. Lancet 2011; 378: 169–81
TIME FOR A SHIFT IN THINKING?
TYPE 2
Shift happens...
According to the Oxford English Dictionary, a shift is defined as: a change in position, direction or tendency
A paradigm shift is described as: a radical change in underlying beliefs or a complete change in thinking or belief systems that allows the creation of a new condition previously thought impossible or unacceptable.
Ridiculous?
As a new paradigm or truth emerges it passes through three distinct stages:
• Firstly, it is ridiculed• Secondly, it is violently opposed • Thirdly, it is accepted as being self-evident.
So here goes then…
An Integrative ApproachIQ SQ
MENTAL SPIRITUAL
PQ EQ
PHYSICAL EMOTIONAL
Case Study
The shape of things to come?
Lifestyle choices
Case study (Male)
THEN• Height: 1.83m• Weight: 105kg• BMI: 31.3• Waist: 107cms• RBP: 148/98• RHR: 76bpm• FBG: 6.3• Mood: Very low• Vitality: None
NOW• Height 1.83m• Weight: 91kg• BMI: 27.2• Waist 100cms• RBP: 106/74• RHR: 48bpm• FBG: 4.7• Mood: Much higher• Vitality: LOADS
Exposed
A Whole-Hearted Approach
Hyperglycaemia• Most of the microvascular complications of
diabetes are related to the degree and the length of exposure to hyperglycaemia.
• New data from the follow-up studies of the Diabetes Control and Complications Trial- the Epidemiology of Diabetes Intervention and Complications Study (DCCT- EDIC), and the United Kingdom Prospective Diabetes Study (UKPDS) emphasize the role of glycaemic control early in the course of the disorder and its value in prevention of later complications.
Legacy Effect
• The phenomenon of ongoing beneficial effects on diabetic complications after a period of improved glycaemic control, even if followed by a return to usual (often poorer) metabolic control, has been described as representing “metabolic memory” by the DCCT/EDIC investigators and as a “legacy effect” by the UKPDS investigators.
Legacy
• According to the Oxford English Dictionary a legacy is:
‘Anything left to or handed down from an ancestor or predecessor...’
DCCT and EDIC• The Diabetes Control and Complications Trial (DCCT)
was designed to test the glucose hypothesis and determine whether the complications of type 1 diabetes (T1DM) could be prevented or delayed.
• The Epidemiology of Diabetes Interventions and Complications (EDIC) observational follow-up determined the durability of the DCCT effects on the more-advanced stages of diabetes complications including cardiovascular disease (CVD).
Conventional v Intensive Treatment• The DCCT (1982–1993) was a controlled clinical trial
in 1,441 subjects with T1DM comparing intensive therapy (INT), aimed at achieving levels of glycaemia as close to the non-diabetic range as safely possible, with conventional therapy (CON), which aimed to maintain safe asymptomatic glucose control.
• INT utilized three or more daily insulin injections or insulin pump therapy guided by self-monitored glucose.
• EDIC (1994–present) is an observational study of the DCCT cohort.
Metabolic Memory• The DCCT followed >99% of the cohort for a mean of 6.5
years and demonstrated a 35–76% reduction in the early stages of microvascular disease with INT, with a median HbA1c of 7%, compared with CONV, with a median HbA1c of 9%.
• The major adverse effect of INT was a threefold increased risk of hypoglycaemia, which was not associated with a decline in cognitive function or quality of life.
• EDIC showed a durable effect of initial assigned therapies despite a loss of the glycaemic separation (metabolic memory) and demonstrated that the reduction in early-stage complications during the DCCT translated into substantial reductions in severe complications and CVD.
Healthy Prospects...
• DCCT/EDIC has demonstrated the effectiveness of INT in reducing the long-term complications of T1DM and improving the prospects for a healthy life span.
UKPDSAlthough the UKPDS set out to determine whether any class of anti-diabetic agent had advantages or disadvantages, the use of multiple therapies made such assessment difficult.
• What was clear from UKPDS was:– early intervention is necessary– ongoing adjustment of therapy is required to prevent
progressive deterioration of blood glucose control– multiple agents are often needed to achieve optimal
blood glucose control– choice of drug therapy should be individualised
UKPDS 2• Given the natural history of type 2 diabetes it is
conceivable that its onset could be prevented if the early rise in insulin secretion was avoided
• In general, clinical symptoms and patient presentation for medical intervention occur late in the disease when fasting hyperglycaemia is already present
• Implications for pre-diabetes and patient responsibility for active engagement and ‘taking it seriously’
Causes of hyperglycaemia• Not enough or bad insulin or oral diabetes medication• Eating or drinking more carbohydrate than usual• Less activity or exercise than usual• Illness or infection (cold, urinary tract infection, heart
attack)• Injury or surgery• Pain• Stress• Any change in normal daily routine• Certain medications• Poor absorption of insulin at injection sites • Insulin pump, insulin pen or meter (device issues)
BALANCE
From this/that to and/both...
Behaviour...
Autonomic IntegrationHigher Centres
Hypothalamus
Medullary Centres
SNS PNS
+
+ ReceptorAfferents
Cognitive
Affective
Psychomotor
Complex or Complicated?
A matter of perspective...
EMOTIONAL TURMOIL
As quickly as possible call out the COLOUR of the words....
GREEN
BLACK
BLUE
DIABETES
RED
SEX
RELEEF
MONEY
PINK
MORON
ORANGE
INSULIN
PURPLE
YELLOW
LEGACY
BLACK
GREEN
CYAN
ORANGE
From Chaos to Coherence
It’s all about...
ENERGY BALANCE
On the wrong track?
Memory and habit
• If you keep doing what you always did you’ll keep getting what you always got!
• We are what we repeatedly do...• Gene expression is based upon emotional
interpretation of environmental cues
STRESS!!!
More than our genes...• Type 2 diabetes is now pandemic and shows no
signs of abatement• Substantial evidence is now emerging indicating
that a major part of diabetes susceptibility is acquired early in life, probably owing to foetal or neonatal programming via epigenetic phenomena.
• Maternal and early childhood health and behaviour might, therefore, be crucial to the development of effective prevention strategies
Ancestry.com• There is now considerable evidence that the
foetal and early postnatal environment also strongly influence the risk of developing such diseases in later life.
• Furthermore, there is increasing evidence of a strong interconnectivity between genetic pre-dispositions, epigenetic processes, stress-related hormonal systems and immune parameters in all forms of (mal)-adjustment to adverse living conditions.
Heredity and Cardiometabolic Disease
• Recent studies have identified certain ‘susceptibility genes’.
• ‘Heredity loads the gun BUT behaviour pulls the trigger’!
Hereditary influences…
The Evidence
Functional teratogenesis
Perinatal programming
Quality of Life
Health: Well-informed
Quality of Life
Disease: Ill-informed?
Progress?
Survival advantage?
THE END
• Research has shown that young children cannot identify the intimate couple because they do not have prior memory associated with such a scenario.
• Children see nine dolphins.• This is a test to determine if you
already have a corrupted mind. • If it is hard for you to find the
dolphins within six seconds, your mind is indeed corrupted.
Say what you see! Quickly
