DOES THE

THE METABOLIC SYNDROME:

DOES I

T

E

XIST

IN

AFRI

CANS IN TRANSI

T

ION

IN

THE NORTHWEST PROVINCE

ANNAMARIE KRUGER (M.Soc.Sc. )

Thesis submitted for the degree ofPhilosphiae in the School ofPhysiology, Nutrition and Consumer Sciences of the Potchefstroomse Universiteit vir

Cluistelike Hoer Onderwys.

Promoter: Prof H.H. Vorster Pu vir CHO

Co-Promoter: Prof B.M. Margetts

ACKNOWLEDGEMENTS

To God Almighty all the glory for giving me the capability and strength to complete this work through very difficult circumstances.

The follovving people need a special \vord of gratitude:

1. Prof. H.H. Vorster for her skilful and inspiring leadership, help and motivation.

' j Prof. B.M. :tY1argetts (University of Southampton) for the education in using the SPSS­

statistical program to analyse the THUSA data and his help in the statistical analyses and interpretation of the data in this study.

3. The \\hole THLSA -research team (36 - 50 researchers and field workers) \vho travelled from site to site throughout the Northwest province for two and a half years (1996-1998). Like any other \\orthy eyent this study could not haw been a success without an excellent skipper (Prof I LH. Vorster). and the loyalty. dedication and hard \\ork of everybody on board.

4. The friendly personnel of the ferdinand Postma library, PU for CHE. for the excellent inter-library sen ices to obtain all the rele\'ant literature.

5. Prof. H.S. Steyn from the statistical services of the PU for CHE for his help with some of the statistical analyses.

6. Mrs. M. Gerber, English teacher, Potchefstroom Gimnasium, for the linguistic editing.

7. .r-vly family: To my husband Gert and two daughters Susan and Karlien for their unconditional support.

ABSTRACT

THE METABOLIC SYNDROME: DOES IT EXIST IN

AFRICANS IN TRANSITION IN THE NORTHWEST

PROVINCE?

Student: Annamarie Kruger

Promoter: Prof. HH Vorster (pU for CHE, Potchefstroom, SA) Co-promoter: Prof. BM Margetts (University of Southampton. UK)

Background:

The term 'metaholic syndrome' is lIsed to dcscribe the clustering in a person of risk factors 'which is associated with the chronic diseases of lifestyle. Considerable evidence exists that insulin resistance is the uJ1(\crlying common factor in the development of the metabolic syndrome. At present. urbanisation occurs very rapidly in the South African population. According to the literatun:. urbanisation is accompanied by the adoption of Western lifestyles and dietary hahits. Therefore. O\crnutrition. the prevalence of risk factors. morhidity and mortality from chronic diseases of lifestyle arc e\:pected to increZtse among urbani sing communities.

Ob.icctiYCs:

1. The questions addressed \\ere whether thc metabolic syndrome exists in the African popubtion of the Nortlmcst province and if it does. what are the characteristics of this syndrome in this population?

J The hypothesis tested in this study \\as that despite the concept of "healthy

obesity" in hlack women (Walker Cl a/.. 1991) the metabolic syndrome will also

develop in black South Africans when they adopt Western lifestyles, Study design:

This study \vas pali of the larger THUSA-study. THUSA was a cross-sectional study of 1854 "apparently healthy"African men and women volunteers, recruited from 3 7 randomly selected sites in the Northwest province and stratified for age. gender and level of urbanisation. A sub-sample of all the fasted SUbjects. 193 men and 233 women. between the ages of 15 and 65 years was selected to imestigate the characteristics of the metabolic syndrome.

Research methods:

A variety of research techniques were used by a multidisciplinary team to collect the data. The results were statistically analysed by using the SPSS 9.0 programme, performing non-parametric statistical tests. Spearman's correlations \""ere used to identify relationships between risk factors of chronic diseases of lifestyle and insulin sensitivity. The GLM Multivariate procedure was used to investigate interactions between risk markers for the chronic diseases of lifestyle and the insulin sensitivity index. Cross-tab statistics were used to calculate odds ratios. Logistic regression analyses were used to investigate the influence of lifestyle factors in the development of the metabolic syndrome. These relationships were used to investigate conditional probabilities in the predicth'e value of \'ariables for early detection in the development of the metabolic syndrome.

Results:

The inllucnce of urbanisation on this population was retlected in a deterioration in lipid profiles, an increased body mass index: (Bi\lI) and percentage body fat (calculated from girths), increased iron status and an increase in insulin resistance.

Although age \\as il1\'Crsely associated with insulin sensitivity in the women, no linear association bet\\een insulin resistance and age was found. An increase in serum urea lewis in women \\as associated \\itb insulin resistance which should be further invcstigated as it may hold a key bctween kidney function and hypertension in African women. A progresshe increase in the risk factors for type 2 diabetes (NIDDM), coronary heart disease (CHD) and obesity was detected in these subjects from a condition of high insulin sensitivity to\vards high insulin resistance. However, these risk factors were still \vithin the boundaries of normal ranges (Chapter 6).

Clusters of two and more (up to five in men and six in women) traditional risk factors for the metabolic syndrome were also found in these "apparently healthy" subjects. Clustering of two and more risk factors occurred in 25% of the men and in 32% of the v'omen. These clusters of risk factors \\ere found despite the absence of insulin resistance. although clusters of more than t\\O risk factors occurred more frequently in

the insulin resistant subjects.

Serum total cholesterol seemed to be a predictor for the clustering of risk factors at levels higher than 4.4 mmollL in men and 4.8 mmollL in women. However, large confidence intervals were observed and results should be interpreted with care. Physical activity seemed to be protectiyc against the clustering of risk factors in the women. Raised plasma fibrinogen lcvcls seemed to be ilwohcd in the developing of insulin resistance in the women and in the clustering of risk factors in the men. High consumption of food energy seemed to be indicative of the development of insulin resistance in the womcn while in the men it seemed to be protective against the clustering of risk factors. This contradiction might be an indication of the importance of food composition rather than quantity in thc deyelopmcnt of the metabolic syndrome. or it could be related to the fact that "ovcrnutrition" as indicatcd by a mean 8\1/ of 26.9 kg/mc was present in the \vomen. while "undernutrition" (mean 8MI of 20.5 kgim2) was more prcvalent in the men. An increase in energy intake would represent further overnutrition in \vomen. while in men it \\ould result in more adequate or optimal nutrition.

Conclusions:

• Insulin resistance and the clustering of risk factors occurred in the study population. Insulin resistance was not the underlying common factor in all the clusters of risk factors for the metabolic syndrome in these subjects. Therefore, the term "multiple metabolic syndrome."suggested by Liese et

at

(1998). will probably be more appropriate to use for this study population.

• Obesity and an inactive lifestyle seem to be risk factors for the development of insulin resistance and a"multiple metabolic syndrome" in these women of the study population.

Recommendations:

The results of this study emphasised obesity as a risk factor in the development of chronic diseases of lifestyle and the importance of physical activity and its protective role against the clustering of risk factors of chronic diseases in black women. Physical activity does not necessarily implicate gymnasium exercises or participation in sport, but also includes walking, dancing and physical labour. In the men the emphasis \\'as on "healthy" or adequate nutrition. Proper education on the benefits of an active lifestyle and

healthy food choices should be included in health intervention programmes. The data generated in this study provides a platform for future research programmes to define criteria for suitable health intervention programmes for the Northwest province. The study raised a number of questions that should be addressed in future research:

1. Evaluation of appropriate cut-off values for total serum cholesterol and serum ferritin levels to predict risk profiles for the development of the "multiple metabolic syndrome" in the Africans of the Nortlnvest province.

} Serum urea as the possible link between insulin resistance and hypertension in black women. needs to be investigated.

3. The optimum dietary composition to be protective against the development of the "multiple metabolic syndrome" in this population should be investigated. 4. The involvement of fibrinogen in the de\'elopment of the metabolic syndrome in

this population should be investigated in more detail.

ABSTRAK

DIE METABOLIESE SINDROOM:

KOMDITVOOR

TYDENS DIE VERSTEDELIKING VAN AFRIKANE IN DIE

NOORDWES PROVINSIE?

Student: Annamarie Kruger

Promotor: Prof. H1-1 Vorster (PU vir ClIO, Potchefstroom)

l\1ede-promotor: Prof. BM Margetts (Universiteit van Southampton. VK)

Agtcrgrond:

Die term 'metaooJicsc sindroom' \yord gcbruik om in '11 persoon die voorkoms van 'n

\I.?rsamcling \an risikofaktorc \\at gcassosiccr kan \\orc! met chroniese le\\enstylsiektetoestande

tc bl.?skryf. BI.?\\yse bestaan dat die onderJiggende gesamentlike faktor in al hierdie sicktetoestande, wat deel uitmaak van die metaboliese sindroom, insulien\\eerstand blyk te wees, Vcrstcdeliking \ind tans teen 'n \innige tempo in die Suid-Afrikaanse be\'oIking plaas, Volgens

die litcratuur gaan verstedeliking gcpaard met die aan\'aarding \an Westerse Ieet\\yse en cetge\\oontcs, Oon'oeding, stygende \'oorkoms \'an risikofaktore vir chroniesc siektl.?s. mortalitdt en morbiditeit kan dus in gemecnskappe wat \erstl.?delik verwag word.

Doelstcllings:

1, Die \Tae \\'aarop antwoordc gesol.?k is. \\as of die metaboliese sindroom in die

Afrikane \an die Noord".ies pro\insie \\'at in 'n proses van \'I.?rwestering is voorkom en indien \\eL \Vat is die kenmerke van hierdie sindroom in die spesifieke populasie?

2, Die hipotese wat in hierdie studie ondersoek is. v;as dat tenspyte van die konsep

van "gesonde oorgewig" in swart \Touens (Walker el al., 1991), die metaboliese sindroom weI in s\\'art vrouens wat 'n westerse lewenswyse aanleer sal ontwikkel.

Studic-ontwcrp:

Hierdie studie was deel \'(m die grotl.?r THUSA-studie THUS A \vas 'n dwarssnitstudie \'an 1854 "oenskynlik gesonde" swart manlike en vroulike \Tywilligers wat gewerf is uit

37 ewekansig geselekteerde plekke in die Noorwes provinsie en gestratifiseer is volgens ouderdom, geslag en vlak van verwestering. 'n Kleiner steekproef van al die vastende proefpersone, 193 mans en 233 vrouens tussen die ouderdomme van 15 en 65 jaar is ingesluit in hierdie studie waarin die kenmerke van die metaboliese sindroom ondersoek

IS.

Navorsingsmetodes:

"n Verskeidenheid nayorsingstegnieke is deur 'n multidissiplinere span gebruik om data te versame!' Die resultate is met nie-parametriese statistiek met behulp van die SPSS 9.0 pakket verwerk. Spearman-korrelasiekoeffisicnte is gebruik om verwantskappe tussen risikofaktore vir chroniese lewenstylsiektes en insuliensensitiwiteit te identifiseer en die ""GLM Multi\'ariate" prosedurc om interaksies lussen die risikomerkers van die chroniese lewenstylsiektes en die insuliensensitiwiteitsindeks te bepaal. Oorkruis tabllieringstalistieke. "n stapsgc\\'yse meervoudige. liniere regressie-analise en logistiese regressie-analises is gebruik om voonvaardelike voorspellingswaardes aan risikomerkers toe te ken ten eindc \Toegtydig die ont\vikkeling \'an die metaboliese sindroom te kan \oorspcl.

f{esuJta tc:

Die indoed yan \'C\"westering op hierdie pOPlllasie is weerspieel in '\1 \'crswakkende

lipiedprofiel. \erhoogde liggaamsmassa-indeks en persentasie liggaamsvet ( bereken dem van omtrekke gebruik te maak), \'erhoogde ysterstatus en "n verhoogde insul ienweerstand.

Geen reglynige verband tussen insulienvveerstand en ouderdom kon gevind vvord nie, ten spyte van die negatievve korrelasie tussen insuliensensitiwiteit en ouderdom wat in die vrouens waargeneem is. "n Verhoogde serum-meumvlak in hierdie vrouens was positief verwant aan 'n insulienweerstand wat verder ondersoek te behoort word, daar dit moontlik lig kan werp op die moontlike verband tussen nierfunksie en hipertensie in swart vrouens. 'n Geleidelike verhoogde risiko vir tipe 2 diabetes, koronere hartvatsiektes en obesitieit is in hierdie proefpersone bespeur vanaf 'n toe stand waar insuliensensitiwiteit prominent is tot vv'aar insulienweerstand ter sprake is. Hierdie risikofaktore was egter steeds binne die normale reik\\"ydtcs (Hoofstuk 6).

Die voorkoms van twee en meer tradisionele risikofaktore vir die metaboliese sindroom (tot vyf in mans en ses in vrouens) is in 25% van die mans en 32% van die vrouens in hierdie "oenskynlik gesonde" proefpersone gevind. Alhoewel hierdie "opstapeling" van risikofaktore In een persoon meer geredelik 111 die teenwoordigheid van insulienweerstand voorgekom het het dit ook voorgekom in die afwesigheid daarvan.

Totale serumcholesterolvlakke van bo 4.4 mmollL in mans en 4.8 mmollL in vrouens het 'n voorspellcr vir die ontwikkeling van die metaboliese sindroom geblyk te wees. Groot vertrouensintervalle is egter vv'aargeneem en resultate moet vcrsigtig geYnterpreteer word.

In die vrouens het fl?i~sgflktiwi!eit 'n beskermende 1'01 gespeel teen die ontwikkeling van die metabolil'se sindroom. I I oe-:plasmafiQrinogel'nvlakke het geblyk 'n rol te speel in die ont\\ikkeling \'an insulienweerstand in die vrouens en die metaboliese sindroom in die mans. In mans was "n hoc-energil'-innamc beskermcnd teen die ontwikkeling van die metaboliesl' sindroom. Daat1ecnoor het 'n hoc-energie-inname inslllienweerstand in die \TOliellS benmicr. Hierdie oenskynlike paradoks clui waarskynlik op die bl'langrikheid

van die samcstelling \al1 \,{ledse! in die ontwikkcling \'an die metabolicse sindroom eerder as die hoc\cdheid wat ingenl'eIll word. Dit kan l'gtl'r ook herlei \\ord tot die feit dat "oorvoeding," SODS geYmpliseer deur 'n gemiddclde liggaamsmassa- indeks van 26.9

kg:m: in die \TOllens en "ondcn'oc?ding:' (gemiddelde liggaamsmassa-indeks van 20.5

kg/mC) in die mans voorgekom het. 'n Hoer energic-innamc sal waarskynlik tot wrdere obesiteit in die \TOUenS lei. terwyl dit in die mans tot" 11 \erbetcring in \'oedingstatus sal

lei.

Gc\'olgtrekkings:

• Insulienweerstand sowel as die metaboliese sindroom het 111 hierdie populasie voorgekom.

• Insulienweerstand was nie die onderliggende gemeenskaplike faktor in nlle gevalle waar

"opeenstapeling" van risikofaktore vir die metaboliese sindroom in 'n persoon voorgekom het nil'. Daar ,",,:ord dus voorgestel dat die gebruik van die term "metaboliese sindroonf' in hierdic studiepopulasie vervang word met "n meer beskrywende term naamlik die "meervoudige metaboliese sindroom" soos \'oorgcstel deur Liese ef

• Qbesiteit en 'n onaktiewe lewens\vyse blyk risikofaktore te wees in die ontwikkeling van beide insulienweerstand en die "meervoudige metaboliese sindroom" in hierdie vrouens.

Aanbevelings:

Die bevindinge in hierdie studie het bevestig dat obesiteit, ook in swart vrouens, as 'n risikofaktor vir chroniese lewenstylsiektes beskou kan word en ook dat 'n aktiewe lewenstyl belangrik is in die voorkoming van die "meervoudige metaboliese sindroom" in swart vrouens. 'n Fisies-aktiewe lewenstyl impliseer nie noodwendig oefeninge in 'n gimnasium of dee1name aan 'n georganiseerde sport nie, maar sluit ook stap, dans en fisiese arbeid in. In die mans het die bevindinge die k1em laat val op gesonde voeding en voedingstatus. Effektiewe onderrig in die voordele van 'n aktiewe lewenstyl en gesonde eetgewoontes moet derhalwe ingesluit word in gesondheidsbevorderende programme. Die inligting wat in hierdie studie bekom is kan met vrug gebruik word in daarstel van su1ke programme vir die Noordwes provinsie. Die inligting kan ook gebruik word om die volgende aanbevelings aangaande verdere navorsing te maak:

• Die vasstelling van toepuslike nOl11mIe reibvydtes vir totale serlll11cholestero1, en -ferritin vir die gebruik as voorspellers in die onhvikkeling \'an die meervoudige metaboliese sindroom in hierdie popu1asie. moet verder ondersoek word. • Die betrokkenheid van serumurelll11 in die ontwikkeling van hipertensie In

insulienweerstandbiedende swart vrouens moet verder ondersoek word.

• Die optimule dieetsamestelling vir hierdie populasie wat beskermend kan wees teen die ontwikkeling van die meervoudige metaboliese sindroom behoort ondersoek te word.

• Die ro1 \vat fibrinogeen in die ontwikkeling van die "meervoudige metaboliese sindroom" in hierdie populasie speel, behoort verder ondersoek te word.

T ABLE OF CONTENTS ACKNOWLEDGEMENTS ABSTRACT ABSTRAK LIST OF TABLES LIST OF FIGliRES DEFINITIONS ABBREVIATIONS CHAPTER 1: Il'iTRODliCTION 1.1 Background 1.2 The problem 1.3 Scientific objectives

1.-+

Enunciation of the study

CHAPTER 2: LITERATllRE REVIEW

2.1 Introduction

') Insulin resistance

2.2.1 Expression of insulin resistance/sensitivity

7 ') 7 Physiology

Pathophysiology: Association of insulin resistance with risk factors of chronic diseases of lifestyle

2.2.4 Gender and population differences

5 Influences of lifestyle

Characteristics of the metabolic syndrome 2.4 Urbanisation of South African blacks

2.4.1 Introduction

2.4.2 The African population of the Northwest province of South Africa 2.4.3 Urbanisation 2.4.3.1 Rural IX Page v xv xviii xix xx 1 4 4 6 6 6 6 7 II 12 I3 16

20

20

20

22 22

2.4.3.2 2.4.3.3 2.4.3.4 2.4.3.5 2.4.4 CHAPTER 3:

3.1

3.4

3.5

3.5.1

3.5.1.1

3.5.1.2 3.5.2.1 3.5.2.2

3.5.3

3.5.3.1

3.5.4

3.5.4.1 3.5.4.2 3.5.5 3.5.5.1 3.5.5.3 3.5.5.4

3.5.5.5

Urban Migration Acculturation

The urbanisation process

Expected health impact of urbanisation

METHODS Introduction Study design Subjects Exclusion criteria Research methods

Questionnaires and intenie\vs

Recruitment of subjects and informed consent Demographic and socio-economic data

Phvsical examination Clinical examination Anthropometric measurements Calculation of indices Anthropometric indices Biochemical indices Sample collection

Method of sample collection Glucose tolerance test Biochemical analyses Serum glucose Serum insulin Serum lipogram Blood haematocrit Plasma fibrinogen x 22 22 22 23 25

26

26

27

27

28

28

28

30 30 31 31

32

.,., .J.J 34 34 34 35 35 35

3.5.5.6

3.5.6

CHAPTER 4: 4.1 4.1.1 4.1.2 4,1.3 4,1.4 4.1.4.1 4.1.4.2 -f.]

A.3

4.2

4.2, \

4.2.2

4,2.3 -+'2 A -L2.5

4,2.6

4,] CHAPTER 5:

Additional biochemical analyses Statistical analyses

RESULTS: GENERAL INFORMATION

Limitations of the study Introduction

Bias

The role of chance

The effect of confounders

HIV-infection as a possible confounder Urbanisation as a possible confounder Other possible confounders

Results: Data stratified by level of urbanisation Personal information

iv1arkers of NIDDM per lc~vel of urbanisation iV1arkcrs of CHD per level of urbanisation i\1arkcrs of obesity pcr Icvel of urbanisation Serum excretion products per level of urbanisation Scrum iron level per level of urbanisation

The intluence of urbanisation on the insulin sensitivity index Discussion and conclusions

RESULTS AND DISCUSSION

THE ASSOCIATION BETWEEN INSULIN RESISTANCE AND RISK FACTORS OR MARKERS OF CHRONIC DISEASES OF LIFESTYLE

5.1 5.2

5.3

5.3.1

5.3.2

5.3.3

Introduction Results Discussion Diet Age Obesity indices

35

36

38 38 38 38 39

40

40

41 42 42 42 44 46

49

51 54 54 57

57

57

61 61 62 62 Xl

5.3.4

Serum lipids and lipoproteins

5.3.5

Blood pressure

5.3.6

Serum calcium

5.3.7

Iron status

5.3.8

Serum uric acid

5.3.9

Serum glucose and insulin

5.4

Conclusions

CHAPTER 6: RESUL TS AND DISCUSSION

THE CHARACTERISTICS OF INSULIN RESISTANCE IN THE AFRICANS OF THE NORTHWEST PROVINCE

6.1 Introduction

6.2 Results

6.2.1 General variables of the subjects per insulin sensitivity qual1ile 6.2.2 Insulin sensitivity and risk markers for NfDDM

6.1.3

Insulin sensitivity and risk markers for CHD 6.2.4 Insulin sensitivity and risk markers for obesity

6.2.5 Insulin sensitivity and risk markers of other metabolic disorders

6.3

Discussion

6.3.1 Insulin sensitivity and personal variables on the subjects 6.3.2 Insulin sensitivity and markers ofNIDDM

6.3.3

Insulin sensitivity and markers of CHD

6.3.4

Insulin sensitivity and markers of obesity

6.3.5 Insulin sensitivity and markers of other metabolic disorders

6.4 Conclusion

CHAPTER 7: RESULTS AND DISCUSSION

CLUSTERING OF RISK FACTORS FOR THE METABOLIC SYNDROME 7.1 Introduction 7.2 Results

63

63

64

64

65

66

66

68

68

69

69

74

76

79

81

84

84

84

85

86

87

87

88 88 90 Xll

7.2.1 Results on elevated traditional markers of the metabolic

syndrome

90

7.2.2 Risk estimation of risk markers for insulin sensitivity

92

7.2.3 Clustering of risk factors with insulin resistance as underlying

common factor

94

7.2.4 Prediction of the metabolic syndrome

95

7.2.5 The influence of urbanisation on the development of insulin

resistance and the metabolic syndrome

96

7.2.6 Risk estimation of the influence of lifestyle factors on insulin

resistance and the metabolic syndrome

97

7.3 Discussion

99

7.4 Conclusion

102

CHAPTER 8: CO~CLllSIOl\"S AND RECOMMENDATIONS )03

8.1 Introduction

103

8.2 Conclusions

103

8.2.1 Conclusions on the occurrence of the metabolic syndrome

103

8.2.2 Conclusions on the hypothesis of "healthy obesity"' in black

women 104

8.2.3 Additional conclusions

105

8.3 Recommendations

107

CONGRESS PRESENTATIONS )08

REFERENCES )09

ADDEr\DUM 1: Recruitment and informed consent form

₁₂₇

ADDENDUfv1 2: Information for participating clinic sisters

129

ADDENDUM 3: Information for participating clinic sisters- What is the

132 THUSA project

ADDENDUlv1 4: Clinical investigation (Green form) ₁₃₅

ADDENDUM 5: Demographic questionnaire

137

ADDENDUM 6: Anthropometric form

143

ADDENDUM 7: Feedback form

₁₄₅

ADDENDUM 8: Additional serum results per insulin sensitivity quartile

₁₄₇

LIST OF TABLES Table 2.1 Table 2.2 Table 4.1 a Table 4.1 b Table 4.2a Table 4.2b Table 4.3a Table 4.3b Table 4.4a Table 4Ab Table 4.5a Table 4.5b Table 4.6a Table 4.6b Table 4.7a Table 4.7b Table 4.8 Table 5.1 Table 5.2

Metabolic effects of insulin

Page

8 A summary of some epidemiological studies on the clustering of the metabolic syndrome, with insulin resistance as common

underlying factor 18

Age for the men per level of urbanisation 42

Age for the 'Nomen per level of urbanisation 42

Personal variables for the men per level of urbanisation (age

adjusted) 43

Personal variables for the women per level of urbanisation (age

adj usted) 44

Serum markers for NIDDM of the men per lewl of urbanisation

(age adjusted) 45

Serum markers for NIDDM of the women per level of urbanisation

(age adjusted) 45

Markers for CHD of the men per level of urbanisation (age adjusted)

47

Markers for CEO of the women per level of urbanisation (age adjusted)

48

Markers for obesity of the men per level of urbanisation (age

adjusted) 49

Markers for obesity of the women per level of urbanisation (age

adjusted) 50

Serum excretion products of the men per level of urbanisation (age

adjusted) 51

Serum excretion products of the women per level of urbanisation

(age adjusted) 52

Iron status of the men per level of urbanisation (age adjusted) 53 Iron status of the women per level of urbanisation (age adjusted) 53

Insulin sensitivity index per level of urbanisation 54

Significant correlations between insulin sensitivity and measured

variables for men 58

Significant correlations between insulin sensitivity and measured

variables for women 60

Table 6.1 Table 6.2a Table 6.2b Table 6.3a Table 6.3b Table 6.4a Table 6.4b Table 6.5a Table 6.5b Table 6.6a Table 6.6b Table 6.7a Table 6.7b Table 6.8a Table 6.8b Table 6.9a Table 6.9b Table 6.10 Table 6.11 a Table 6.11 b Table 6.12a Table 6.12b

Quartiles of the insulin sensitivity index 69

Personal variables for the men per quartile of insulin sensitivity 70 Personal variables for the women per quartile of insulin sensitivity 71

Lifestyle markers for the men 72

Lifestyle markers for the women 73

Markers for NIDDM of the men per quartile of insulin sensitivity 74 Markers for NIDDM of the men per quartile of insulin sensitivity

(after adj ustment for age, energy and alcohol intake) 75 Markers for NIDDM of the women per quartile of insulin

sensitivity

75

Markers for NIDDrvI of the women per quartile of insulin

sensitivity (after adjustment for age, energy and alcohol intake) 76 T.",1arkers for CHD of the men per quartile of insulin sensitivity

Markers for CHD of the men per quartile of insulin sensitivity

(after adjustment for age, energy and alcohol intake) 77 Markers for CHD of the women per quartile of insulin sensitivity 77 Markers for CHD of the women per quartile of insulin sensitivity

(after adjustment for age. energy and alcohol intake) 78 Markers for obesity of the men per quartile of insulin sensitivity 80 Markers for obesity of the men per quartile of insulin sensitivity

(after adjustment for age. energy and alcohol intake) 80 Markers for obesity of the women per quartile of insulin sensitivity 81 Markers for obesity of the women per quartile of insulin sensitivity (after adjustment for age, energy and alcohol intake) 81 Serum excretion products of the men per quartile of insulin

sensitivity 82

Serum excretion products of the women per quartile of insulin

sensi ti vi ty 82

Serum excretion products of the women per quartile of insulin

sensitivity (after adjustment for age, energy and alcohol intake) 82 Iron status of the men per quartile of insulin sensitivity 83 Iron status of the men per quartile of insulin sensitivity (after

adjustment for age, energy and alcohol intake) 83

Table 6.13 Table 7.1 Table 7.2 Table 7.3 Table 7.4 Table 7.5 Table 7.6 Table 7.7 Table 7.8 Tahle 7.9 Table 7.10 Table 7.11 Table 7.12

Iron status of the women per quartile of insulin sensitivity 84 Traditional risk factors/markers for the metabolic syndrome 89 A summary of the percentage of elevated risk markers for the

metabolic syndrome

90

Stepwise regression analysis for the men 91

Stepwise regression analysis for the women 91

Risk estimation of risk markers associated with insulin resistance for the men

92

Risk estimation of risk markers associated with insulin resistanee

for the women 93

The clustering of risk factors of the metabolic syndrome

94 Predictive value of risk markers for the metaholic syndrome for the men

95

Predictiw yalue of risk markers for the metaholic syndrome for the

women 95

The influence of urbanisation on the clustering of risk factors

96

Significant influences of lifestyle factors on the development of

insulin resistance in the men and women 98

Significant influences of lifestyle factors on the clustering of risk factors in the development of the metaholic syndrome in the men and women

98

LIST OF FIGURES Figure 2.1 Figure 2.2 Figure 2.3 Figure 2.4 Figure 2.5 Figure 3.1 Figure 7.1 Figure 7.2 Page

Illustration of the events involved in insulin stimulated glucose

transport in muscle and adipose cells 9

Some mechanisms of receptor-mediated insulin resistance 10 Some mechanisms of post-receptor-mediated insulin resistance 10

The role of insulin resistance in the clustering of risk factors 17

Expected health outcomes of urbanisation 24

The arm of the subjects were immobilised in a splint 33 Illustration of the influences of insulin resistance on the

clustering of risk factors in the men and women 94

Illustration of the influence of urbanisation on the clustering of

risk factors 97

DEFINITIONS:

For the purpose of this study the following terms are defined as:

Metabolic syndrome: The clustering of risk markers for NIDDM, CHD and obesity with insulin resistance as common underlying factor (Reaven, 1988). 2. Insulin sensitivity: A high insulin index as calculated by 10 000 + [fasting insulin

(/.1U/ml)

X fasting glucose (mmoIlL)]. (Donahue et al., 1988). QuartiJes of the insulin sensitivity index

~ender Insulin sensitivity Quartiles Donahue et al., 1988 Quartile ranJle Std. Deviation N ~en 1 Low sensitivity <=113 30.3 33

2 :>113 <=149.5 11 A 33

3 :>149.5 <=191.5 12.0 34

4 High sensitivity :>191.5 37.1 33

, ~omen 1 Low sensitivity <=87.7 18.5 44 I

2 :>87.7 <= 117.5 8.8 44 3 :>117.5 <=158.95 12.2 44 4 High sensitivity :>158.95 61.04 44 I 3. Insulin resistance: 4. Africans:

The relationship between fasting glucose and insulin is the basis of calculation of insulin sensitivity.

When both glucose and insulin leyels arc low. a high insulin sensiti\'ity index indicates that low glucose levels can be maintained with 10\.\ insulin.

In this study. subjects who fell in the top quartile (4) of the insulin sensitivity index distributions. \\'ere classified as being insulin sensiriye.

An alternative expression for a decreased insulin sensitivity (Colagiuri and Brand Miller, 1997).

When both glucose and insulin levels are high, the insulin sensitivity will be low, indicating that despite a high insulin secretion, low (natural) blood glucose levels cannot be maintained. This condition is referred to as insulin resistance. In this study, subjects who fell in the bottom quartile (l) of the insulin sensitivity index distributions, were classified as being insulin resistant.

Black (Negroid) South Africans

LIST OF ABBREVIATIONS: ARIC-study BD BMI BP CHD CHS CVD cm Creat DBP OM DNA Fe FE satur FFA Fib g g/d Glue To GlucT1: o GLM GTT Hc ·HDL-C I-lip-max HIV IGT IHD lRAS IR IS IS Ql IS Q2 IS Q3 IS Q4 IU!1

KJ

Kg Kg/m2 LD LDL-C LDLHDL med mm

Atherosclerosis Risk in Communities Body density

Body mass index Blood pressure

Coronary heart disease Cardiovascular Health Study Cardiovascular disease Centimetres

Creatinine

Diastolic blood pressure Diabetes mellitus Deoxyribonucleic acid Iron

Iron saturation Free fatty acids Fibrinogen Gram

Gram per decilitre Fasting glucose Two hour glucose General linear model Glucose tolerance test Haematocrit

High-density lipoprotein Maximum hip circumference Human immunodeficiency virus Intolerant glucose test

Ischemic heart disease

Insulin Resistance and Atherosclerosis Study Insulin resistance

Insulin sensitivity

Insulin sensitivity quartile 1 Insulin sensitivity quartile 2

Insulin sensitivity quartile 3

Insulin sensitivity quartile 4 International units per litre Kilojoules

Kilogram

Kilogram per square metre Litre

Lactate dehydrogenase

Low-density lipoprotein cholesterol

Low-density lipoprotein, high-density lipoprotein ratio Medium

Millimetres

xx

MMS mmHg mmol/L . n NAS NRC NIDDM

P

PI PAl R S SBP st. SD Sig Stats Stratum 1 Stratum 2 Stratum 3 Stratum -1­ TB T-Bili TC

TG

TIBC THUSA uSA VLDL Waist-hip min WHO WHR Y % ,umollL ,uUIL

°c

Multiple metabolic syndrome Millimetres of mercury Millimol per litre Number I sample size

National Academy of Science, National research Council Non-insulin-dependent diabetes mellitus

Probability (level of significance) Plasma

Plasminogen activator inhibitor Rand (currency)

Serum

Systolic blood pressure Standard or education grade Standard deviation

Significance Statistics

Urbanisation level: rural

Urbanisation level: farm living subjects urbanisation level: squatter dwellers

urbanisation level: urban and upper urban citizens Tuberculosis

Total bilirubin Total cholesterol Triglycerides

Total iron binding capacity

Transition and Health during urbanisation of South Africans United States of America

Very low density lipoprotein Minimum waist circumference World Health Organisation Waist to hip ratio

Years Percentage

Micro mol per litre Micro units per litre Degree Celsius