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Altered Glucose and Lipid Metabolism

In persons with SCI, the usual clinical measures of total body fat, such as weight and body mass index (BMI), underestimate the degree of adiposity (Bauman et al. 1997; Mollinger et al. 1985; Spungen et al. 1993; Spungen et al. 2000; Spungen et al. 2003). The metabolic alterations related to adverse body composition changes, decreased physical activity and other factors in individuals with SCI are considered atherogenic (Maki et al. 1995; National Cholesterol Education Program 2001, 2002). Even a mild decline in glucose tolerance is associated with insulin resistance and hyperinsulinemia, which are also considered atherogenic (Haffner et al. 1990).

Table 4 Lipid Lipoprotein Profiles

Low-density lipoprotein (LDL)·   Lipid protein complex that transports cholesterol from the liver to other tissues within the body. LDL is often referred to as the “bad” cholesterol. LDL levels above 160 mg/dL (4.1 mmol/L) are considered to be high.
High-density lipoprotein (HDL)·   Lipid protein complex that transports cholesterol from the tissues to the liver for excretion and re-utilization. HDL is often referred to as the “good” cholesterol. HDL levels of <40 mg/dL (<1.03 mmol/L) are associated with an increased risk for CVD.
Total cholesterol (TC)·     Total amount of all cholesterol in the blood (increased TC related to increased risk for CVD)
Triglycerides (TG)·     High energy fatty acids which form much of the fat stored by the body

 

Many factors contribute to increased risk of insulin resistance and hyperinsulinemia, glucose intolerance, CVD and obesity in persons with SCI. These factors tend to correlate with the severity and level of the neurological deficit (Javierre et al. 2005). It is hypothesized that the decreased lean muscle mass and increased adipose tissue which follow a SCI lead to impaired glucose uptake and an imbalance in whole body glucose homeostasis (Javierre et al. 2005). Pathogenesis of SCI combined with lifestyle practices impact blood glucose management thereby increasing the risk of morbidity and mortality due to CVDs, a frequent cause of death among persons with SCI (Arrowwood et al. 1987; Javierre et al. 2005; Yekutiel et al. 1989). Abnormalities in lipid metabolism in SCI develop early following injury and tend to progress over time (Brenes et al. 1986; Bauman et al. 1992; Kocina 1997; Szlachcic et al. 2001). Insulin resistance and exaggerated hyperinsulinemia in response to an oral glucose challenge are associated with the development of type II diabetes mellitus, atherosclerosis and ischemic heart disease (Bauman et al. 1992; Defronzo et al. 1991; Duckworth et al. 1983; Mohr et al. 2001). Conventional risk factors for coronary heart disease should be identified and treated aggressively in individuals with SCI according to current standards of care (Bauman & Spungen 2008).

Table 5 Altered Glucose and Lipid Metabolism

Author Year

Country
Research Design

PEDro Score
Total Sample Size

MethodsOutcome
Glucose
Battram et al. 2007
Canada
RCTPEDro=6N=14
Population: Mean age=44.9 yr; Mean weight=82.1 kg; Level of injury: C4-C6; Level of severity: AIS A=5, AIS B and C=9; Mean time since injury=15.0 yr.

Intervention: Participants were randomized to receive a 4 mg/kg dose of caffeine capsule or gelatin placebo capsules. Both groups then consumed a standard 75 gram glucose solution, and then a oral glucose tolerance test (OGTT) was performed. Analyses were performed between intervention groups, and subgroup analyses between SCI severity (complete vs. incomplete).

Outcome Measures: Glucose response area under the curve (AUC), Insulin levels, Proinsulin levels, Proinsulin to insulin (PI/I) ratio, glucagon-like-peptide-1 (GLP-1), Epinephrine concentrations, Free fatty acid levels, glycerol concentrations, Mean arterial pressure (MAP),

1.     The caffeine and placebo groups were not significantly different in glucose response AUC during the OGTT (p>0.05).

2.     The complete SCI subgroup had a 50% greater glucose response AUC compared with the incomplete SCI subgroup (p<0.05).

3.     Proinsulin levels were 40% lower in the complete group compared to the incomplete group (p<0.05).

4.     There were no treatment or subgroup effects on insulin levels (p>0.05), proinsulin levels or PI/I ratio (p>0.05), GLP-1 (p>0.05), epinephrine concentrations (p>0.05), free fatty acid (p=0.07), glycerol (p>0.05),

5.     The caffeine group had a significantly higher MAP compared to the placebo group (p<0.05).

Effect Sizes: Forest plot of standardized mean differences (SMD ± 95%C.I.) as calculated from pre- and post-intervention data.

Bennegard & Karlsson 2008

Sweden

Prospective Controlled Trial

N=19

Population: SCI (n=9): Mean age=40.8 yr; Mean weight=71.2 kg; Level of injury: C=2, T=7; Severity of injury: AISA A=8, B=1; Non-SCI controls (n=10): Mean age=31.9 yr; weight=75.9 kg.

Intervention: Blood flow and overnight fasting glucose.

Outcome Measures: Glucose uptake, plasma flow, lean tissue mass, and lactate.

1.     SCI individuals were found to have significantly higher glucose uptake than those in the control group (p<0.05).

2.     Plasma flow was higher in legs of SCI individuals than the controls.

3.     Control subjects had higher lean tissue mass in their legs compared to the SCI subjects who only had 2/3 of the lean mass of the control subjects.

4.     For non-SCI individuals glucose uptake was lower in legs than arms in the control group whereas venous glucose concentration was higher in the leg (p<0.05); no differences were observed for those with SCI.

5.     Control subjects had a higher lactate production in arms than legs (p<0.05), while SCI subjects did not.

Bauman & Spungen 1994

USA

Cohort

N=150

Population: Paraplegia (n=50): Mean age=51±2 yr; Time since injury=19±2 yr; Tetraplegia (n=50): Mean age=47±2 yr; Time since injury=17±2 yr; Controls (n=50): Mean age=51±2 yr; SCI and controls were age- and BMI-matched.

Intervention: Oral glucose tolerance test (OGTT).

Outcome Measures: Mean plasma glucose and insulin values, serum lipid levels.

1.      82% of controls had normal oral glucose tolerance vs. 38% of those with tetraplegia and 50% with paraplegia.

2.      Subjects with SCI had significantly higher mean glucose and insulin values during the OGTT when compared to controls.

3.      Serum lipid levels in subjects with SCI showed a decreased HDL cholesterol level (38±1 mg/dL).

Bauman et al. 1999

USA

Pre-Post

N=201

Population: Mean age=39 yr; Gender: males=169, females=32; Mean duration of injury=13 yr; Mean weight=75.9 kg; Mean BMI=25; Level of injury: tetraplegia=81, paraplegia=120; Severity of injury: complete=140, incomplete=61.

Intervention: Oral glucose tolerance test (OGTT).

Outcome Measures: Serum glucose concentration, plasma insulin levels, hyperinsulinemia, and serum uric acid.

1.     Individuals with complete tetraplegia had higher values for serum glucose concentration at 60 min, 90 min and 120 min and for plasma insulin at 90 min and 120 min after OGTT.

2.     Levels of serum glucose were similar in both men and women; however, plasma insulin levels were greater in men than women at all time points (p<0.05).

3.     Individuals with complete tetraplegia also had an increased frequency of diabetes mellitus compared to others.

4.     Individuals with tetraplegia had a significantly higher rate of hyperinsulinemia than individuals with paraplegia (p<0.05).

5.     A significant relationship was found between serum uric acid and BMI (p<0.0001), peak serum glucose (p=0.001) and peak plasma insulin (p=0.01).

Lipid
Ketover et al. 1996

USA

Prospective Controlled Trial

N=58

Population: SCI (n=29): Mean age=51 yr; Gender: males=28, females=1; Obesity (BMI>27)=11; Non-SCI controls (n=29): Mean age=36 yr; Gender: males=13, females=16; Obesity (BMI>27)=14.

Intervention: All individuals were administered a 20 g fat liquid meal.

Outcome Measures: Gallbladder emptying.

1.      No significant difference was seen in gallbladder emptying and volumes between SCI individuals and non-SCI subjects.

2.      In SCI subjects with diabetes and obesity, poor gallbladder emptying was observed.

3.      Age and injury level had no effect on gallbladder emptying.

Note: AISA=ASIA Impairment Scale; BMI=Body Mass Index

Discussion

Four studies have examined altered glucose metabolism in individuals after a SCI (Bauman et al. 1999; Bauman & Spungen 1994; Bennegard & Karlsson 2008, Battram et al. 2007). Significantly higher serum glucose concentration and diabetes mellitus was seen in persons with complete tetraplegia than any other classification of SCI (Bauman et al. 1999). Gender had no effect on level of serum glucose; however, men had greater insulin levels than women (p<0.05; Bauman et al. 1999). In the remaining two studies, fasting glucose levels were compared between individuals with and without SCI. Bauman and Spungen (1994) reported that 38% and 50% of individuals with tetraplegia and paraplegia, respectively, had normal oral glucose tolerance compared to 83% of the non-SCI control group. Their findings were supported by Bennegard and Karlsson (2008) who reported a significantly higher glucose uptake in individuals with SCI compared to non-SCI controls. Those with SCI had higher plasma flow rate in their legs compared to the controls; however, lean tissue mass was lower than those without SCI (Bennegard & Karlsson 2008). Battram et al. (2007) found that caffeine ingestion does not impair glucose tolerance in tetraplegics as well.

Recent research has begun to examine the altered glucose response in relation to visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). Gorgey and Gater (2011) examined 32 males with SCI (mean body mass=74±14 kg; mean BMI=23.5±4.5) after an overnight glucose fast and found that both leg and trunk fat mass were associated with an altered metabolic profile. Further, those with tetraplegia (n=7) had greater leg, trunk and body fat mass than those with paraplegia (n=25). Fasting glucose was higher and the resting metabolic rate was 18% lower in those with tetraplegia than in those with paraplegia (p<0.05). Similarly, Gorgey et al. (2011) assessed VAT and SAT among 13 males with SCI (mean body mass=74±13 kg; mean BMI=23±4) after an overnight glucose fast. The authors reported that individuals with VAT >100 cm2 had higher fasting plasma glucose compared to those with <100 cm2; further, VAT and SAT were associated with an altered metabolic profile. Although Gorgey and Gater (2011) and Gorgey et al. (2011) have presented a connection between fat mass and altered glucose response in individuals with SCI, the findings were conflicted with regard to lipid profile.

Altered lipid metabolism is apparent in the SCI population. In a prospective controlled trial, Ketover et al. (1996), evaluated gallbladder emptying in non-SCI individuals compared to persons with SCI after administering liquid meal (20 g fat). Both groups demonstrated similar gallbladder emptying and volumes post interventions; however, diabetic and obese subjects with SCI showed poor gallbladder emptying (Ketover et al. 1996).

There are a significant number of other biochemical changes in serum concentrations that occur after a SCI. Studies that examine these trends without specific regard to nutritional status or intervention have been placed in either the Aging Chapter or Cardiovascular Chapter. Please review those chapters for further exploration of resting glucose, insulin, lipid and other blood levels post SCI.

Conclusion

There is level 2 evidence (from one prospective controlled trial and one cohort study; Bennegard & Karlsson 2008; Bauman & Spungen 1994) that glucose uptake is higher in paralysed, spastic legs of SCI subjects than in able-bodied controls. There is a regional difference in glucose uptake in able-bodied with a lower uptake in legs than in arms.

There is level 2 evidence (from one cohort study and one pre-post study; Bauman & Spungen 1994; Bauman et al. 1999) that SCI individuals with tetraplegia have higher rates of altered glucose metabolism than other SCI individuals.

There is level 2 evidence (from one prospective controlled trial; Ketover et al. 1996) that diabetic and obese SCI individuals show impaired gallbladder emptying in response to a high fat meal compared to healthy SCI individuals.

  • Individuals with tetraplegia have higher rates of altered glucose metabolism.

  • Impaired gallbladder emptying is seen in diabetic and obese SCI individuals.